6 Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[,

CPF CRRNKECVKQP

-CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

#DUVTCEV

(QT Kluyveromyces lactis DCUKE TGUGCTEJ, FGXGNQROGPV QH IGPGVKE VQQNU CPF KPFWUÿ
VTKCN CRRNKECVKQP JCU IQPG JCPF KP JCPF QXGT VJG NCUV HKHVGGP [GCTU. 6JKU CTVKENG
UWOOCTK\GU VJG EWTTGPV MPQYNGFIG YKVJ RCTVKEWNCT GORJCUKU QP IGPGVKEU CPF
RJ[UKQNQI[ KP EQORCTKUQP VQ Saccharomyces cerevisiae. 6JG K. lactis IGPQOG UGÿ
SWGPEKPI RTQLGEV KU ENQUG VQ EQORNGVKQP CPF JCU CNTGCF[ UJQYP VJCV, KP EQPVTCUV VQ
S. cerevisiae, KPVGPUKXG IGPG FWRNKECVKQPU CTG NCEMKPI YJGTGCU C TGRGTVQKTG QH IGPGU
PQV RTGUGPV KP S. cerevisiae EQPHGTU C DTQCFGT UWDUVTCVG URGEVTWO. /CTMGF FKHHGTÿ
GPEGU GZKUV YKVJ TGURGEV VQ TGIWNCVKQP QH ECTDQP OGVCDQNKUO CPF VJG DCNCPEG DGÿ
VYGGP HGTOGPVCVKQP CPF TGURKTCVKQP. K. lactis RTQXGF UWKVCDNG CU C JQUV HQT TGEQOÿ
DKPCPV RTQVGKP RTQFWEVKQP FWG VQ NQY RTQVGCUG NGXGNU, JKIJ HQNFKPI CPF UGETGVKQP
ECRCEKV[, CPF VJG CDUGPEG QH C %TCDVTGG GHHGEV. )GPGVKE CPCN[UKU CPF IGPGVKE OQFKÿ
HKECVKQP ECP DG RGTHQTOGF CU KP S. cerevisiae CPF VJG CXCKNCDNG VQQNU CTG IGVVKPI KPÿ
ETGCUKPIN[ GNCDQTCVG.

6.1 +PVTQFWEVKQP

+PFWUVTKCN KPVGTGUV KP Kluyveromyces lactis KPKVKCNN[ HQEWUUGF QP GP\[OGU, KP RCTÿ

VKEWNCT NCEVCUG, YJKEJ YGTG RWTKHKGF HTQO VJKU [GCUV CPF WUGF KP DKQEQPXGTUKQP
RTQEGUUGU. 6JWU, HGTOGPVCVKQP VGEJPQNQI[ KU YGNN GUVCDNKUJGF CPF VJG )4#5 þgGPÿ
GTCNN[ rGICTFGF aU sCHGý UVCVWU YCU CRRTQXGF VQ GP\[OGU RTGRCTCVKQPU HTQO K. lac-
tis CNNQYKPI VJGO VQ DG WUGF CU HQQF CFFKVKXGU. #OQPI VJQUG CTG TGEQODKPCPV GPÿ
\[OGU HTQO IGPGVKECNN[ GPIKPGGTGF UVTCKPU VJCV JCXG DGEQOG CXCKNCDNG CHVGT C
DCVVGT[ QH IGPGVKE VQQNU JCF DGGP FGXGNQRGF. 0QYCFC[U, K. lactis DGNQPIU VQ VJG
DGUVÿGUVCDNKUJGF PQPÿSaccharomyces [GCUVU HQT YJKEJ DCUKE CU YGNN CU CRRNKGF TGÿ
UGCTEJ KU IQKPI JCPF KP JCPF.
1XGT VJG RCUV HKHVGGP [GCTU, Kluyveromyces TGUGCTEJ JCU DGPGHKVGF HTQO RWDNKE
HWPFKPI CPF C UOCNN DWV CEVKXGN[ KPVGTCEVKPI UEKGPVKHKE EQOOWPKV[ VJCV OGGVU QPEG
C [GCT CV XCT[KPI NQECVKQPU YKVJKP ©WTQRG. 9G YKUJ VQ FGFKECVG VJKU TGXKGY CTVKENG
VQ *KTQUJK (WMWJCTC YJQ YCU C HQWPFGT CPF EGPVTCN OQVQT QH VJKU EQOOWPKV[ CPF
YJQ UVKNN KU C XGT[ CEVKXG UWRRQTVGT QH Kluyveromyces TGUGCTEJ. 6JCPMU VQ /QPKSWG
$QNQVKPÿ(WMWJCTC þ2CTKUý YJQ OCPCIGF VQ OCMG TGCN VJG K. lactis IGPQOG UGÿ
SWGPEKPI RTQLGEV CV )oPQUEQRG þ(TCPEGý. K. lactis TGUGCTEJ YKNN UQQP GPVGT VJG
RQUVÿIGPQOKE GTC, YJKEJ WPFQWDVGFN[, D[ EQORCTKUQPU YKVJ VJG TGHGTGPEG [GCUV S.
Topics in Current Genetics, Vol. 2
J.H. de Winde (Ed.): Functional Genetics of Industrial Yeasts
Springer-Verlag Berlin Heidelberg 2003
ü7û -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

cerevisiae, YKNN RTQXKFG XCNWCDNG KPUKIJV KPVQ IGPQOG GXQNWVKQP, OQNGEWNCT RJ[UKÿ
QNQI[, CPF IGPGVKEU.
# PWODGT QH TGXKGY CTVKENGU QP K. lactis JCXG DGGP RWDNKUJGF TGEGPVN[
þ9oUQNQYUMKÿúQWXGN GV CN. üùùø÷ $TGWPKI GV CN. ûööö÷ 5EJCHHTCVJ CPF $TGWPKI,
ûööö÷ $QNQVKPÿ(WMWJCTC GV CN. ûöööý CPF C OCPWCN QP GZRGTKOGPVCN OGVJQFU KP K.
lactis TGUGCTEJ KU CXCKNCDNG þ9QNH GV CN. ûöö3ý. 6JKU EJCRVGT YKNN VJGTGHQTG HQEWU QP
VJG OQUV TGEGPV NKVGTCVWTG GORJCUK\KPI KP RCTVKEWNCT FKHHGTGPEGU DGVYGGP K. lactis
CPF S. cerevisiae.

6.2 )GPGVKEU

6.2.1 ÿCZQPQO[ QH Kluyveromyces UUR. CPF RJ[NQIGPGVKE TGNCVKQPUJKR

VQ S. cerevisiae

6CZQPQOKE ENCUUKHKECVKQP QH Kluyveromyces species JCU C JKUVQT[ QH EJCPIGU.

Kluyveromyces lactis DCUGF QP KVU CDKNKV[ VQ WVKNKUG NCEVQUG YCU KPKVKCNN[ ENCUUKHKGF
CU Saccharomyces lactis. úCVGT QP, RJ[UKQNQIKECN ETKVGTKC, NKMG VJG RGVKVGÿPGICVKXG
EJCTCEVGT, VJG %TCDVTGG GHHGEV, CPF VJG KPCDKNKV[ VQ ITQY CPCGTQDKECNN[, UGRCTCVGF
VJG IGPWU Kluyveromyces HTQO Saccharomyces. /QNGEWNCT V[RKPI VGEJPKSWGU HKÿ
PCNN[ UGV Kluyveromyces lactis CRCTV HTQO K. marxianus CPF K. fragilis KPVQ C UGRCÿ
TCVG URGEKGU þ8CWIJCPÿ/CTVKPK GV CN. üùù3÷ -WTV\OCP CPF 4QDPGVV üùùõý.
6JG HKGNFU QH OKETQDKCN VCZQPQO[ JCXG DGGP TGXQNWVKQPK\GF UKPEG IGPQOKE UGÿ
SWGPEGU DGECOG CXCKNCDNG. 6JG EQORNGVKQP QH VJG S. cerevisiae IGPQOG UGSWGPEG
KP üùùø RTQXKFGF CP KPXCNWCDNG CPEJQT RQKPV HQT EQORCTCVKXG HWPICN IGPQOKEU CPF
GWMCT[QVKE GXQNWVKQP. Kluyveromyces lactis CPF KVU TGNCVKXGU DGNQPI VQ C ITQWR HQT
YJKEJ EQORCTCVKXG CRRTQCEJGU CTG RCTVKEWNCTN[ KPHQTOCVKXG. (KTUV KPUKIJV KPVQ VJG
K. lactis IGPQOG QTICPKUCVKQP YCU RTQXKFGF D[ 1\KGTÿ-CNQIGTQRQWNQU GV CN. YJQ
UGSWGPEGF ôôõ TCPFQO UGSWGPEG VCIU þ456Uý þ1\KGTÿ-CNQIGTQRQWNQU GV CN. üùùõý.
6JKU CRRTQCEJ YCU GZVGPFGF KP VJG )GPQNGXWTG + RTQLGEV, C HWPICN IGPQOG UGÿ
SWGPEKPI KPKVKCVKXG QH GKIJV (TGPEJ TGUGCTEJ KPUVKVWVKQPU, KP YJKEJ ü3 JGOKCUEGVQÿ
O[EVQWU [GCUVU KPENWFKPI K. lactis YGTG CPCN[UGF þ5QWEKGV GV CN. ûööö÷ úNQTGPVG GV
CN. ûöööC÷ úNQTGPVG GV CN. ûöööD÷ $QNQVKPÿ(WMWJCTC GV CN. ûöööý. #DQWV ûôöö 14(U
JCXG DGGP KFGPVKHKGF QH YJKEJ ûô GPEQFG PGY RTQVGKPU YKVJ PQ QTVJQNQIWGU KP S.
cerevisiae þ$QNQVKPÿ(WMWJCTC GV CN. ûöööý. /QUV QH VJGUG OC[ TGRTGUGPV GP\[OGU
KPXQNXGF KP OGVCDQNKE RCVJYC[U CNNQYKPI K. lactis VQ CUUKOKNCVG ECTDQP CPF PKVTQÿ
IGP HTQO UQWTEGU VJCV CTG PQV WUGF D[ S. cerevisiae. +PVTQPU CTG UECTEG CU KP S. cer-
evisiae; UGSWGPEGU YKVJ UKOKNCTKV[ VQ VTCPURQUQPU 6[ü CPF 6[û JCXG DGGP HQWPF QP
LWUV C HGY ©56U.
6JGTG KU C TGOCTMCDNG UKOKNCTKV[ KP IGPG QTFGT þU[PVGP[ý DGVYGGP VJG K. lactis
CPF VJG S. cerevisiae IGPQOGU þ1\KGTÿ-CNQIGTQRQWNQU GV CN. üùùõ÷ -GQIJ GV CN.
üùùõý. #DQWV ôùó QH CFLCEGPV IGPG RCKTU KP K. lactis QT K. marxianus CTG CNUQ CFÿ
LCEGPV KP S. cerevisiae, CPF C HWTVJGT üøó QH Kluyveromyces PGKIJDQWTU ECP DG GZÿ
RNCKPGF KP VGTOU QH VJG KPHGTTGF CPEGUVTCN IGPG QTFGT KP Saccharomyces RTKQT VQ VJG
QEEWTTGPEG QH CP CPEKGPV YJQNGÿIGPQOG FWRNKECVKQP. /QTGQXGT, GZVGPUKXG IGPG
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ü73

FWRNKECVKQPU CTG PQV HQWPF KP VJG K. lactis IGPQOG FGURKVG VJG HCEV VJCV UQOG UKPÿ
INGÿEQR[ IGPGU QH S. cerevisiae JCXG FWRNKECVGU KP K. lactis þ$QNQVKPÿ(WMWJCTC GV
CN. ûöööý. 6JGUG UGSWGPEG GXCNWCVKQPU JCXG NGCF VQ VJG UWIIGUVKQP VJCV K. lactis FKÿ
XGTIGF HTQO VJG S. cerevisiae NKPGCIG DGHQTG VJG RTQRQUGF IGPQOG FWRNKECVKQP QEÿ
EWTTGF CPF OC[ VJWU DG ENQUGT VQ VJG VTWPM QH VJG RJ[NQIGPGVKE VTGG þ9QNHG CPF
5JKGNFU üùù7÷ -GQIJ GV CN. üùùõ÷ 5GQKIJG CPF 9QNHG üùùù÷ 2KUMWT ûööüý. /QTG
FGHKPKVG RTQQH KU GZRGEVGF HTQO VJG )oPQNGXWTG ++ RTQLGEV EWTTGPVN[ KP RTQITGUU,
YJKEJ KU GZRGEVGF VQ [KGNF VJG EQORNGVG K. lactis IGPQOG UGSWGPEG DGHQTG ûööò.

6.2.2 %JTQOQUQOGU CPF GZVTCEJTQOQUQOCN IGPGVKE GNGOGPVU

6.2.2.1 Centromeres and telomeres on the six -. NCEVKU chromosomes

6JG JCRNQKF IGPQOG QH K. lactis EQPUKUVU QH UKZ EJTQOQUQOGU TCPIKPI KP UK\G HTQO
ü.ü þHQT VJG UOCNNGUV EJTQOQUQOG +ý VQ û.ø /DR þ/.$QNQVKPÿ(WMWJCTC, RGTUQPCN
EQOOWPKECVKQPý. 6JG HQWTVJ EJTQOQUQOG EQPVCKPU VJG T&0# TGRGCVU CPF CRRGCTU
UQOGVKOGU FKHHWUG CPF RQQTN[ UGRCTCVGF HTQO EJTQOQUQOG 8 KP RWNUGÿHKGNF IGN
GNGEVTQRJQTGUKU. # PWODGT QH IGPGU OCRRGF D[ ENCUUKECN IGPGVKE OGVJQFU YGTG CUÿ
UKIPGF VQ EJTQOQUQOGU D[ J[DTKFKUCVKQP þ9oUQNQYUMKÿúQWXGN CPF (WMWJCTC
üùùôý. # OQTG GZVGPUKXG OCRRKPI QH $#% ENQPGU VQ KPFKXKFWCN EJTQOQUQOGU JCU
TGEGPVN[ DGGP HKPKUJGF CU RCTV QH VJG )oPQNGXWTG ++ RTQLGEV.
(KXG QH VJG UKZ EGPVTQOGTGU JCXG DGGP ENQPGF D[ VJGKT CDKNKV[ VQ EQPHGT UVCDNG
VTCPUOKUUKQP VJTQWIJ OKVQUKU QH #45 EQPVCKPKPI &0# CU NQY EQR[ GRKUQOGU. %GPÿ
VTQOGTKE XGEVQTU JCXG DGGP FGTKXGF HTQO VJG ENQPGF K. lactis EGPVTQOGTGU CPF
UJQYP VQ DG UVCDN[ OCKPVCKPGF KP üÿû EQRKGU RGT EGNN. 6JG EGPVTQOGTGU CTG QTICPÿ
KUGF KP C UKOKNCT YC[ CU KP S. cerevisiae CPF EQPVCKP VJG EQPUGTXGF GNGOGPVU %&©+,
%&©++, CPF %&©+++ . 6JG #6ÿTKEJ %&©++ KU CDQWV VYKEG CU NQPI CU KP S. cerevisiae
CPF VJWU VJG UK\G QH VJG EGPVTQOGTGU KU CDQWV ûôö DR. &GURKVG UKOKNCT QTICPKUCVKQP,
K. lactis EGPVTQOGTGU CTG WPCDNG VQ EQPHGT EGPVTQOGTG HWPEVKQP KP S. cerevisiae CPF
vice versa þ*GWU GV CN. üùùò CPF TGHGTGPEGU VJGTGKPý. 5RGEKGU URGEKHKEKV[ CRRGCTU VQ
DG C EQOOQP HGCVWTG QH EGPVTQOGTG HWPEVKQP GXGP HQT ENQUGN[ TGNCVGF URGEKGU. 4Gÿ
OCTMCDN[, EGPVTQOGTGU HTQO Kluyveromyces marxianus YGTG UJQYP VQ HWPEVKQP KP
K. lactis þ+DQTTC CPF $CNN üùùòý.
6JG OQNGEWNCT DCUKU HQT URGEKGU URGEKHKEKV[ JCU PQV DGGP GNWEKFCVGF. 6JG NGPIVJ
FKHHGTGPEG KP %&©++ KU WPNKMGN[ VQ DG TGURQPUKDNG þ*GWU GV CN. üùùò ý. *QYGXGT,
VJGTG KU OWEJ TQQO HQT URGEKHKEKV[ KP VJG NCTIG RTQVGKP EQORNGZ VJCV HQTOU GXGP QP
VJG UOCNN EGPVTQOGTGU QH DWFFKPI [GCUVU þ%NCTMG üùùõ÷ -KVCICYC CPF *KGVGT
ûööüý. 6JG %&©+++ DKPFKPI EQORNGZ YJKEJ PWENGCVGU VJG MKPGVQEJQTG QH S. cere-
visiae EQPUKUVU QH 0FEüöñ%DHû, %GR3, %VHü3, CPF 5MRü. KlSKP1 YCU ENQPGF D[
UWRRTGUUKQP QH C S. cerevisiae ctf13-ts OWVCPV CPF UJQYP VQ DG CP GUUGPVKCN IGPG,
CU GZRGEVGF þ9KPMNGT GV CN. ûöööCý. #VVGORVU VQ KUQNCVG C NDC10/CBF2 JQOQÿ
NQIWG D[ EQORNGOGPVCVKQP QH C cbf2-ts OWVCPV HCKNGF. +PUVGCF, OWNVKÿEQR[ UWRRTGUÿ
UQTU GPEQFKPI WDKSWKVKP EQPLWICVKPI CPF WDKSWKVKP J[FTQN[UKPI GP\[OGU YGTG
HQWPF þ9KPMNGT GV CN. ûöööDý. KlCBF1 GPEQFKPI VJG %&©+ DKPFKPI EQORQPGPV YCU
CNUQ UJQYP VQ EQORNGOGPV VJG EQTTGURQPFKPI S. cerevisiae OWVCVKQP CPF vice
ü7ò -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

versa þ/WNFGT GV CN. üùù3÷ 9KPMNGT GV CN. ûöööC÷ 9KPMNGT GV CN. ûöööDý. CBF1 KU CP
GUUGPVKCN IGPG KP K. lactis DWV PQV KP S. cerevisiae þ/WNFGT GV CN. üùù3ý. +V KU RQUUKÿ
DNG VJCV VJG GUUGPVKCN HWPEVKQP KP K. lactis KU PQV TGNCVGF VQ EGPVTQOGTG HWPEVKQP DWV
VQ UQOG QVJGT CURGEV QH VJG OWNVKHWPEVKQPCN %DHü RTQVGKP, YJKEJ KU CNUQ KPXQNXGF KP
IGPG TGIWNCVKQP þ/GNNQT GV CN. üùùö÷ /WNFGT GV CN. üùùôDý.
6GNQOGTGU, VJG PCVWTCN GPFU QH GWMCT[QVKE EJTQOQUQOGU, CTG GUUGPVKCN HQT VJG
RTQVGEVKQP QH EJTQOQUQOGU HTQO GPFÿVQÿGPF HWUKQP. 6JG K. lactis VGNQOGTGU JCXG
DGGP CPCN[UGF GZVGPUKXGN[ KP VJG NCD QH ©NK\CDGVJ $NCEMDWTP þ/E©CEJGTP GV CN.
ûöööý. +P EQPVTCUV VQ VJG KTTGIWNCT S. cerevisiae TGRGCVU, VJG[ EQPUKUV QH üô VCPFGO
EQRKGU QP CXGTCIG QH C RGTHGEV ûôÿDR TGRGCV VJCV EQPVCKPU VJG üû DR EQPUGPUWU UGÿ
SWGPEG HQT 4CRü, C EQPUGTXGF VGNQOGTG DKPFKPI HCEVQT þ(KI. üý.

5'-)#66#))6#6)6))6)6#%))#666-3'
3'----###%7##7%%#7#%#%%#%#7)%%7###%7-----5'

(KI. 1. K. lactis 6GNQOGTKE 4GRGCV. 6JG ûô DR VGNQOGTKE TGRGCV KU UJQYP KP VJG WRRGT NKPG
YKVJ VJG 4CRü DKPFKPI UKVG KP KVCNKEU. 6JG NQYGT NKPG TGRTGUGPVU VJG EQFKPI RCTV QH VGNQOGTKE
40# GPEQFGF D[ VJG TER1 IGPG, WPFGTNKPGF CTG HNCPMKPI FKTGEV TGRGCVU. #HVGT /E©CEJGTP
GV CN. þûööûý.

6JG WPWUWCNN[ NQPI ûôÿDR TGRGCV QHHGTGF VJG RQUUKDKNKV[ VQ UGRCTCVG 4CRü DKPFÿ
KPI HWPEVKQP HTQO HNCPMKPI GHHGEVU. $[ OWVCIGPGUKU QH VJG TER1 IGPG GPEQFKPI VJG
40# RQTVKQP QH VGNQOGTCUG VJG TGRGCV UGSWGPEG JCU DGGP CNVGTGF CPF VWTPQXGT QH
VGNQOGTKE UGSWGPEGU YCU GZCOKPGF. 6JG TGUWNVU UWRRQTVGF VJG ETWEKCN TQNG QH 4CRü
KP VGNQOGTG OCKPVGPCPEG CPF TGRGCV EQR[ PWODGT EQPVTQN þ/E©CEJGTP GV CN. ûööö÷
/E©CEJGTP GV CN. ûööûý.

6.2.2.2 Linear cytoplasmic DNA plasmids conferring the Killer

phenotype
+P UGXGTCN K. lactis UVTCKPU, VYQ FQWDNGÿUVTCPFGF NKPGCT &0# RNCUOKFU JCXG DGGP
FGVGEVGF VJCV EQPHGT C ÉMKNNGTÌ RJGPQV[RG þ)WPIG GV CN. üùõüý. 6JGUG RNCUOKFU JCXG
DGGP GZVGPUKXGN[ UVWFKGF KP UGXGTCN NCDU þ)WPIG üùõø÷ 5VCTM GV CN. üùùö÷ 5EJCHHTCVJ
GV CN. üùùù÷ /GKPJCTFV GV CN. üùù7ý. 6JG[ FKURNC[ C UVTWEVWTCN QTICPKUCVKQP CNUQ
HQWPF KP QVJGT HWPICN NKPGCT RNCUOKFU CPF CTG TGOKPKUEGPV QH XKTWUÿNKMG IGPGVKE
GNGOGPVU. 6JG K. lactis RNCUOKFU CTG UVCDN[ OCKPVCKPGF KP VJG E[VQRNCUO YJGTG
VJG[ CTG TGRNKECVGF CPF VTCPUETKDGF D[ RNCUOKF GPEQFGF RQN[OGTCUGU TGNCVGF VQ OKÿ
VQEJQPFTKCN RQN[OGTCUGU. #P ÉWRUVTGCO EQPUGPUWU UGSWGPEGÌ þð%5ý VJCV KU PQV
TGEQIPKUGF D[ PWENGCT 40# RQN[OGTCUGU FGHKPGU VJG RTQOQVGTU QH VJG RNCUOKF
14(U þ4QOCPQU CPF $Q[F üùõõý.
©CEJ RNCUOKF EQPVCKPU C NCTIG 14( þ6CDNG üý VJCV GPEQFGU C &0#ÿRQN[OGTCUG
þ&02ý CU C HWUKQP RTQVGKP YKVJ C RNCUOKFÿURGEKHKE VGTOKPCNÿGPFÿDKPFKPI RTQVGKP
þ62ý VJCV UGTXGU CU TGRNKECVKQP RTKOGT. 6JG NCTIGT RNCUOKF þMû÷ R)-úûý EQPVCKPU
PKPG CFFKVKQPCN 14(U GPEQFKPI OCKPVGPCPEG HWPEVKQPU KPENWFKPI C RTQVGKP TGSWKTGF
HQT TGRNKECVKQP KPKVKCVKQP, C UKPINGÿUVTCPFGF &0# DKPFKPI RTQVGKP CPF C RWVCVKXG
JGNKECUG. 6JG UOCNNGT Mü þR)-úüý RNCUOKFU ECTT[ QPN[ ò 14(U, VJTGG QH YJKEJ CTG
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ü7ô

TGNCVGF VQ VJG MKNNGT RJGPQV[RG. 14(U û CPF ò GPEQFG VJG MKNNGT VQZKP QT É\[OQEKPÌ,
C VTKOGTKE UGETGVGF RTQVGKP. 6JG !ÿ CPF "ÿUWDWPKVU QH VJG \[OQEKP CTG RTQEGUUGF
HTQO CP !"ÿRTGEWTUQT þMü 14(ûý QH YJKEJ VJG !ÿ UWDWPKV KU 0ÿIN[EQU[NCVGF. 6JG #ÿ
UWDWPKV þÄÿVQZKPý GPEQFGF D[ 14(ò KU VJG E[VQVQZKE FGVGTOKPCPV þ$WVNGT GV CN.
üùùüCýþUGG 5GEVKQP 3.òý. 14(3 KU CP KOOWPKV[ FGVGTOKPCPV QH WPMPQYP OQNGEWNCT
PCVWTG. 9JGTGCU VJG NCTIGT Mû RNCUOKF KU UGNHÿUWUVCKPKPI, Mü TGSWKTGU Mû HWPEVKQPU
HQT OCKPVGPCPEG þ5EJCHHTCVJ GV CN. üùùôý. (QT C OQTG FGVCKNGF FGUETKRVKQP QH VJG
RNCUOKF CPF VJG K. lactis \[OQEKP VJG TGCFGT KU TGHGTTGF VQ C TGEGPV TGXKGY
þ5EJCHHTCVJ CPF $TGWPKI ûöööý.

6CDNG 1. 2TQVGKP EQFKPI IGPGU QP K. lactis MKNNGT RNCUOKFU

PCOG HWPEVKQP 4GHGTGPEG

MüñR)-úü:
14(ü Müÿ62ñ&02 þ-KVCFC CPF )WPIG üùõõý
14(û <[OQEKPþ½¾ý þ5VCTM CPF $Q[F üùõøý
14(3 KOOWPKV[ þ6QMWPCIC GV CN. üùõ7ý
14(ò \[OQEKP þÄý þ$WVNGT GV CN. üùùüD÷6QMWPCIC GV CN. üùõùý
MûñR)-úû
14(ü !
14(û Mûÿ62ñ&02 þ6CMGFC GV CN. üùùø÷6QOOCUKPQ GV CN. üùõõý
14(3 O40# ECRRKPI þúCTUGP GV CN. üùùõý
14(ò JGNKECUG þ5VCTM GV CN. üùùöý
14(ô 55$ þ5EJCHHTCVJ CPF /GCEQEM ûööüý
14(ø 402 þ5EJCHHTCVJ GV CN. üùùô÷9KNUQP CPF /GCEQEM
üùõõý
14(7 402! þ5EJCHHTCVJ GV CN. üùù7ý
14(õ !
14(ù !
14(üö TGRNKECVKQP KPKVKCVKQP þ/E0GGN CPF 6COCPQK üùùü÷ 6QOOCUKPQ üùùüý

5KPEG VJG MKNNGT RNCUOKFU CTG TGOCTMCDN[ KPFGRGPFGPV QH JQUV HWPEVKQPU, VJG[
OC[ HWPEVKQP CU XGEVQTU YKVJ C DTQCF JQUV TCPIG. 2NCUOKF URGEKHKE RTQOQVGTU JCXG
DGGP WUGF VQ FTKXG GZRTGUUKQP QH IGPGVKE OCTMGTU CPF TGEQODKPCPV IGPGU þ5EJKEMGN
GV CN. üùùøý. 6JGUG IGPGU YGTG KPVTQFWEGF KPVQ VJG MüñMû IGPQOG D[ C TGEQODKPCÿ
VKQPÿDCUGF E[VQRNCUOKE UJWHHNKPI U[UVGO þ5EJCHHTCVJ GV CN. üùùùý. *QYGXGT, FGURKVG
VJG JKIJ EQR[ PWODGT þ$ ôöý RTQVGKP NGXGNU YGTG RQQT EQORCTGF VQ PWENGCT GRKÿ
UQOCN RNCUOKFU. ©XGP YJGP 40# NGXGNU YGTG EQORCTCDNG VQ PWENGCT GPEQFGF
VTCPUETKRVU, RTQVGKP NGXGNU YGTG OWEJ NQYGT KPFKECVKPI RQQT VTCPUNCVKQP QH VJGUG
40#U þ4GNKGPG CPF 5CUPCWUMCU üùù7ý.

6.2.2.3 Circular nuclear plasmids

#P CFXCPVCIG QH K. lactis IGPGVKEU CPF DKQVGEJPQNQI[ KU VJG CXCKNCDKNKV[ QH OWNVKÿ
EQR[ GRKUQOCN XGEVQTU. 6JKU IQGU DCEM VQ VJG RKQPGGTKPI YQTM QH (WMWJCTC CPF EQÿ
YQTMGTU YJQ UETGGPGF OCP[ [GCUV URGEKGU HQT ET[RVKE GRKUQOCN RNCUOKFU. 6JG[
HQWPF C ü.ø±OÿRNCUOKF, R-&ü, KP Kluyveromyces lactis var. drosophilarum þ%JGP
GV CN. üùõøý. 6JKU RNCUOKF ECP DG UVCDN[ OCKPVCKPGF KP K. lactis XCT. lactis CPF JCU
ü7ø -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

UKPEG DGGP FGXGNQRGF KPVQ C UGTKGU QH E.coli K. lactis QT E.coli K. lactis S.

cerevisiae UJWVVNG XGEVQTU þ%JGP GV CN. üùõù÷ $KCPEJK GV CN. üùùü÷9oUQNQYUMKÿ
úQWXGN GV CN. üùùøý. 6JG QTICPKUCVKQP QH R-&ü KU UKOKNCT VQ VJCV QH VJG û±Oÿ&0#
QH S. cerevisiae: 6JG TGRNKECVKQP QTKIKP QXGTNCRU YKVJ QPG QH VJG VYQ KPXGTVGF TGÿ
RGCVU CPF VJTGG IGPGU CPF C EKUÿCEVKPI UVCDKNKV[ NQEWU CTG KPXQNXGF KP TGRNKECVKQP,
RCTVKVKQPKPI CPF EQR[ PWODGT EQPVTQN QH VJG GRKUQOG þ$KCPEJK GV CN. üùùüý.

6.2.3 /KVQEJQPFTKCN &0#

6JG UK\G QH VJG OKVQEJQPFTKCN &0# KU CDQWV 3ù MD þ9oUQNQYUMKÿúQWXGN GV CN.

üùùøý CPF UGSWGPEGF OKVQEJQPFTKCN EQPVKIU EQORTKUG CDQWV û7 MD þ$QNQVKPÿ
(WMWJCTC GV CN. ûöööý. #OQPI VJG UGSWGPEGF IGPGU CTG COX1 þE[VQEJTQOG QZKÿ
FCUG UWDWPKV üý, COX2 þUWDWPKV ûý, COX3 þUWDWPKV3ý, ATP9 þUWDWPKV ù QH VJG OKVQÿ
EJQPFTKCN #62CUGý, VAR1 þTKDQUQOCN RTQVGKPý, VJG ûü5 T40# IGPG, CPF UGXGTCN
V40# IGPGU. +PVTQP UGSWGPEGU JCXG DGGP KFGPVKHKGF KP VJG ATP9 CPF ûü5 T40#
IGPG UGSWGPEGU. # PQPCPWENGQVKFG ô'ÿþ#ñ6ý6#6##)6#ÿ3' EQPUGPUWU UGSWGPEG
TGEQIPK\GF D[ VJG [GCUV OKVQEJQPFTKCN 40# RQN[OGTCUGU KU RTGUGPV KP HTQPV QH VJG
VTCPUETKRVKQP WPKVU þ1UKPIC GV CN. üùõûý.
/KVQEJQPFTKCN &0# COQWPVU WR VQ üö ó QH VQVCN EGNNWNCT &0#, UWIIGUVKPI CP
CXGTCIG EQR[ PWODGT QH 3ö þ9oUQNQYUMKÿúQWXGN GV CN. üùùøý. 0WOGTQWU )%ÿTKEJ
ENWUVGTU VJCV CTG TGEQODKPCVKQP JQV URQVU KP S. cerevisiae CTG RTGUGPV KP VJG K. lactis
DWV PQV KP VJG K. marxianus OKVQEJQPFTKCN &0# þ4CIPKPK CPF (WMWJCTC üùõõý.
&GURKVG VJG HCEV VJCV K. lactis KU RGVKVGÿPGICVKXG OKVQEJQPFTKCN &0# ECP TGEQODKPG
CPF IKXG TKUG VQ OV RGVKVGU KP EGTVCKP OWVCPV DCEMITQWPFU þUGG 5GEVKQP 3.3ý

6.2.4 /CVKPI V[RGU

K. lactis FKRQKFU CTG WPUVCDNG CPF URQTWNCVG GXGP QP TKEJ OGFKWO. 6JG RKQPGGTKPI
YQTM QH *CNXQTUQP KP VJG GCTN[ UKZVKGU NCKF VJG ITQWPF HQT VJG IGPGVKEU QH K. lactis
D[ GUVCDNKUJKPI IGPGVKECNN[ OCTMGF UVTCKPU YKVJ FGHKPGF OCVKPI V[RG þ*GTOCP CPF
4QOCP üùøø÷ 9oUQNQYUMKÿúQWXGN GV CN. üùùøý. +UQNCVKQP QH CP !ûÿNKMG IGPG þ;WCP
GV CN. üùù3ý UWIIGUVGF VJCV OCVKPIÿV[RGU CTG EQPVTQNNGF KP C UKOKNCT YC[ CU KP S.
cerevisiae. +PFGGF, UKOKNCTKV[ YCU EQPHKTOGF D[ VJG EJCTCEVGTK\CVKQP QH HML$,
HMRa CPF MAT NQEK þ#UVTQO GV CN. ûöööý. HML CPF HMR NQEK CTG UKNGPEGF KP C
5KTû CPF 5KTò FGRGPFGPV OCPPGT þ#UVTQO CPF 4KPG üùùõý DWV VJGTG CTG C PWODGT
QH FKHHGTGPEGU CU EQORCTGF VQ S. cerevisiae. +P VJG HML$ NQEWU, DGUKFGU VJG VYQ
IGPGU !ü CPF !û TGUGODNKPI VJG S. cerevisiae IGPGU, C VJKTF NQPI 14(, !3 YCU
HQWPF þ#UVTQO GV CN. ûöööý. 6JKU IGPG KU RCTV QH MAT$ DWV KU CNUQ GZRTGUUGF HTQO
HML$ KP ! UVTCKPU. &GNGVKQP QH VJG IGPG TGFWEGF OCVKPI GHHKEKGPE[ DWV VJG RTGUÿ
GPEG QH ½3 CV GKVJGT HML QT MAT YCU UWHHKEKGPV HQT OCVKPI. 6JG RWVCVKXG õù7
COKPQ CEKFU QH !3 FKF PQV TGXGCN CP[ UKOKNCTKV[ VQ IGPGU KP VJG FCVC DCUG. 6JG
HMRC NQEWU EQPVCKPU VYQ IGPGU Cü CPF Cû CPF KPFKTGEV GXKFGPEG UWIIGUVU VJCV KP
FKRQKF EGNNU CP Cüñ!û EQORNGZ GZKUVU VJCV TGRTGUUGU JCRNQKF URGEKHKE IGPGU NKMG KP
S. cerevisiae.
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ü77

#UVTQO GV CN. þ#UVTQO GV CN. ûöööý CNUQ UJQYGF VJCV UKNGPEKPI QH HML YCU FWG
VQ VJG RTGUGPEG QH QPG EKUÿCEVKPI UKNGPEGT HNCPMGF D[ C UGSWGPEG EQPHGTTKPI #45
HWPEVKQP. +V YCU RQUUKDNG VQ FGNGVG VJG #45 YKVJQWV CHHGEVKPI UKNGPEKPI EQPHKTOKPI
VJCV FGURKVG VJG GXQNWVKQPCT[ EQPUGTXCVKQP QH VJKU CTTCPIGOGPV #45 HWPEVKQP KU PQV
CP GUUGPVKCN RTGTGSWKUKVG HQT UKNGPEKPI. 5KNGPEKPI YCU UJQYP VQ DG FGRGPFGPV QP K.
lactis 5KTû CPF VQ C NGUUGT GZVGPV QP 5KTò. 6JG RTGUGPEG QH VJGUG HCEVQTU ETGCVGU C
URGEKCNK\GF EJTQOCVKP UVTWEVWTG CV VJG UKNGPEGTU CU UJQYP D[ VJG TGUKUVCPEG VQ &0#
OGVJ[NCVKQP. +P CFFKVKQP, K. lactis sir2 OWVCPVU CTG J[RGTÿUGPUKVKXG VQ ECVKQPU NKMG
0Kûï CPF %Wûï CPF GVJKFKWO DTQOKFG þ#UVTQO GV CN. ûöööý. 6JG TGNCVKQP QH VJKU
RJGPQV[RG VQ VJG MPQYP 5KTû HWPEVKQP KU PQV WPFGTUVQQF.
#P HO GPFQPWENGCUG IGPG JCU PQV DGGP KFGPVKHKGF UQ HCT. +H KV GZKUVU, KV OC[ DG
GZRTGUUGF CV C XGT[ NQY TCVG KP UQOG UVTCKPU FKURNC[KPI CP CRRCTGPV UVCDNG OCVKPIÿ
V[RG, UKPEG KV JCU DGGP QDUGTXGF VJCV UQOG QH VJGUG UVTCKPU ECP UYKVEJ YKVJ C NQY
HTGSWGPE[ þ<QPPGXGNF, RGTU. EQOOWPKECVKQPý. +V OC[ VJWU DG YKUG VQ WUG VGUVGT
UVTCKPU QH DQVJ OCVKPI V[RGU CPF JKIJ EGNN FGPUKVKGU KP CUUKIPKPI VJG CNNGNKE UVCVWU QH
VJG MAT NQEWU.

6.3 þJ[UKQNQI[

6.3.1 %CTDQP CPF GPGTI[ OGVCDQNKUO

6.3.1.1 Introduction
+P Kluyveromyces lactis, CU KP OQUV QTICPKUOU, IN[EQN[UKU CPF VJG VTKECTDQZ[NKE
CEKF E[ENG CTG VJG OCKP RCVJYC[U HQT VJG WVKNK\CVKQP QH UWICTU CPF VJG IGPGTCVKQP QH
GPGTI[ þ#62ý. 5KOKNCTN[, INWEQUG KU VJG OQUV RTGHGTTGF UWICT, DWV Kluyveromyces
URGEKGU ECP ITQY QP C YKFG XCTKGV[ QH UWICTU CPF QVJGT ECTDQP UQWTEGU. #RCTV HTQO
NCEVQUG, UVTCKPU QH VJKU URGEKGU ECP ITQY HQT KPUVCPEG QP EGNNQDKQUG, OGNG\KVQUG,
Z[NKVQN, OCPPKVQN, NCEVCVG, UWEEKPCVG, DWVCPGÿû,3ÿFKQN þYYY.EDU.MPCY.PNñ[GCUVý, CPF
UGXGTCN COKPQ CEKFU þ<GGOCP GV CN. üùùùý. *QYGXGT, VJKU EJCRVGT YKNN HQEWU QP VJG
WVKNK\CVKQP QH INWEQUG XKC IN[EQN[UKU CPF VJG 6%# E[ENG, YKVJ TGHGTGPEG VQ QVJGT
RCVJYC[U YJGTG CRRTQRTKCVG. /QTGQXGT, HQT JKUVQTKECN TGCUQPU VJGUG RCVJYC[U JCXG
DGGP UVWFKGF OQUV GZVGPUKXGN[ KP Saccharomyces cerevisiae CPF VJGTGHQTG QPN[ VJG
FKHHGTGPEGU YKVJ VJKU [GCUV YKNN DG FKUEWUUGF KP OQTG FGVCKN. # TGEGPV CPF FGVCKNGF
TGXKGY QH VJGUG RCVJYC[U KP UGXGTCN PQPÿSaccharomyces [GCUVU OC[ DG HQWPF
GNUGYJGTG þ(NQTGU GV CN. ûöööý. (KIWTG û KU TGRTKPVGF HTQO VJKU TGXKGY CPF IKXGU C
UWOOCT[ QH ECTDQP CPF GPGTI[ OGVCDQNKUO KP [GCUVU.
K. lactis UVTCKPU JCXG DGGP KUQNCVGF HTQO XCTKQWU UQWTEGU. 6JGUG PCVWTCN KUQNCVGU
XCT[ KP VJGKT RTQRGTVKGU þ$TGWPKI, üùõù÷ )QHHTKPK GV CN.üùõù÷ úQFK GV CN.üùùõý. /QTG
KP FGRVJ UVWFKGU CTG RGTHQTOGF QP C NKOKVGF PWODGT QH UVTCKPU QPN[ CPF %$5û3ôù
JCU DGGP EJQUGP CU VJG RTGHGTTGF UVTCKP HQT IGPGVKE UVWFKGU D[ VJG K. lactis EQOOWÿ
PKV[ VQ OCMG TGUWNVU GZEJCPIGCDNG CPF EQORCTCDNG þ5QWEKGV GV CN. ûööö, 9oUQÿ
NQYUMKÿúQWXGN GV CN. üùùøý. 6JKU UVTCKP ITQYU TCRKFN[ KP FGHKPGF OGFKC YKVJ C IGPÿ
GTCVKQP VKOG QH EC. ùö OKP YKVJ C [KGNF QH ö.ô I FT[ YGKIJVñITCO INWEQUG þ-KGTU GV
CN. üùùõ÷ <GGOCP GV CN. üùùõ÷ <GGOCP GV CN. üùùùý. +P TKEJ OGFKWO þ;2&ý CPF CV
ü7õ -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ü7ù

(KI. ÿ. ;GCUV ECTDQP CPF GPGTI[ OGVCDQNKUO. 6JG HKIWTG TGRTGUGPVU C J[RQVJGVKECN [GCUV
EGNN YKVJ HGCVWTGU HTQO S. cerevisiae CPF QVJGT [GCUVU. 6JG VJKEM NKPG YKVJ DNCEM FQVU TGRTGÿ
UGPVU VJG EQOOQP IN[EQN[VKE VTWPM CPF VJG 6%# E[ENG. &CUJGF NKPGU FGPQVG TGCEVKQPU VJCV
CTG WUGF FWTKPI ITQYVJ KP PQPÿHGTOGPVCDNG ECTDQP UQWTEGU. úKPGU YKVJ FQVU CPF FCUJGU KPÿ
FKECVG VJCV, FGRGPFKPI QP VJG [GCUV IGPGTC, UQOG QH VJG FKUCEEJCTKFGU TGRTGUGPVGF OC[ DG
J[FTQN[\GF QWVUKFG VJG EGNN QT VTCPURQTVGF CU UWEJ KPVQ KV CPF J[FTQN[\GF KP VJG E[VQRNCUO.
%KTENGU KP OGODTCPGU KPFKECVG VTCPURQTV U[UVGOU QT RTQVGKPU NQECVGF KP UWEJ UVTWEVWTGU.
úKPGU IQKPI VJTQWIJ VJG OKVQEJQPFTKCN OGODTCPG FQ PQV PGEGUUCTKN[ KORNKECVG VJCV VJG EQTÿ
TGURQPFKPI OGVCDQNKVG HTGGN[ ETQUUGU KV. 6JG OCNKE GP\[OG KU PQV TGRTGUGPVGF. 0Q QTICPGNNGU
DGUKFG VJG OKVQEJQPFTKQP CTG FTCYP. 6JG HQNNQYKPI PQPÿUVCPFCTF CDDTGXKCVKQPU KP RCVJYC[U
FKHHGTGPV HTQO IN[EQN[UKU JCXG DGGP WUGF: ø2), øÿRJQURJQINWEQPCVG: 4WNô2, TKDWNQUG ôÿ
RJQURJCVG: 4ôR, TKDQUG ôÿ RJQURJCVG÷ îWNô2, Z[NWNQUG ôÿRJQURJCVG÷ 572, UGFQJGRVWNQUG 7ÿ
RJQURJCVG÷ ©ò2, GT[VJTQUG òÿRJQURJCVG÷)32, IN[EGTQN 3ÿRJQURJCVG÷ 2K, 'KPQTICPKE" RJQUÿ
RJCVG÷ 1##, QZCNQCEGVCVG÷ í, WDKSWKPQPG÷ DEü, E[VQEJTQOGU÷ %[V QZ, E[VQEJTQOG QZKFCUG.
4GRTKPVGF HTQO (NQTGU GV CN. þûöööý YKVJ RGTOKUUKQP HTQO ©NUGXKGT.

KVU QRVKOWO ITQYVJ VGORGTCVWTG QH 33·%, VJG IGPGTCVKQP VKOG OKIJV GXGP DG TGÿ
FWEGF VQ 7ô OKP þ5VGGPUOC GV CN. üùõõý. /QUV TGUWNVU FKUEWUUGF DGNQY TGHGT VQ VJKU
UVTCKP CPF KVU FGTKXCVKXGU, WPNGUU UVCVGF QVJGTYKUG.
/CP[ IGPGU KPXQNXGF KP INWEQUG OGVCDQNKUO JCXG DGGP HQWPF KP C UETGGP HQT
OWVCPVU VJCV DGECOG UGPUKVKXG VQ VJG TGURKTCVKQP KPJKDKVQT CPVKO[EKP # KP VJG RTGUÿ
GPEG QH JKIJ INWEQUG EQPEGPVTCVKQPU, VJG 4CIÿ RJGPQV[RG. 5GXGTCN PCVWTCN K. lactis
KUQNCVGU CTG UGPUKVKXG VQ VJKU FTWI, YJGTGCU QVJGTU CTG TGUKUVCPV þ(GTTGTQ GV CN. üùõüý.
6JG TGUKUVCPV UVTCKPU RTQDCDN[ IGPGTCVG UWHHKEKGPV GPGTI[ HTQO HGTOGPVCVKQP VQ UWUÿ
VCKP ITQYVJ. /WVCVKQPU KP IGPGU KPXQNXGF KP IN[EQN[UKU CPF CNEQJQNKE HGTOGPVCVKQP
YKNN FKUCDNG VJKU ECRCEKV[. #V VJG NCVGUV EQWPV, QXGT VYGPV[ 4CIÿ EQORNGOGPVCVKQP
ITQWRU JCXG DGGP HQWPF þ/. 9oUQNQYUMKÿúQWXGN , RGTUQPCN EQOOWPKECVKQPý CPF
VJGUG KPENWFG IGPGU GPEQFKPI UVTWEVWTCN CU YGNN CU TGIWNCVQT[ RTQVGKPU KPXQNXGF KP
IN[EQN[UKU CPF HGTOGPVCVKQP. 5GXGTCN QH VJGUG IGPGU YKNN RCUU D[ KP UWDUGSWGPV UGEÿ
VKQPU QH VJKU EJCRVGT.

6.3.1.2 Glucose uptake

+P EQPVTCUV VQ S.cerevisiae, KP YJKEJ C NCTIG HCOKN[ QH JGZQUG VTCPURQTVGTU KU RTGÿ
UGPV, QPN[ HQWT IGPGU HQT VJG WRVCMG QH JGZQUGU JCXG DGGP HQWPF UQ HCT KP K. lactis.
RAG1 GPEQFGU C WPKSWG QT VJG OCKP NQYÿCHHKPKV[ INWEQUG VTCPURQTVGT KP UQOG
UVTCKPU þ2TKQT GV CN. üùù3C÷ 9oUQNQYUMKÿúQWXGN GV CN. üùùûC÷ 9oUQNQYUMKÿúQWXGN
GV CN. üùùûD÷ )QHHTKPK GV CN. üùùöý, YJGTGCU KP QVJGT UVTCKPU VJKU NQEWU ECTKGU VYQ
VCPFGON[ CTTCPIGF JGZQUG VTCPURQTVGT IGPGU, KHT1 CPF KHT2, YKVJ õòó UGÿ
SWGPEG KFGPVKV[ GCEJ QH YJKEJ EQPHGTU C 4CIï RJGPQV[RG þ9GKTKEJ GV CN. üùù7ý. #NN
VJTGG VTCPURQTVGT IGPGU JCXG JKIJ UGSWGPEG UKOKNCTKV[ CPF KV CRRGCTU VJCV RAG1 JCU
CTKUGP D[ C FGNGVKQP GXGPV DGVYGGP VJG VYQ KHT IGPGU UWEJ VJCV RAG1 KU KFGPVKECN
VQ KHT1 GZEGRV HQT VJG NCUV VJTGG COKPQ CEKFU, YJKEJ QTKIKPCVG HTQO KHT2. (TWEÿ
VQUG CPF ICNCEVQUG CTG CNUQ VCMGP WR D[ VJGUG INWEQUG VTCPURQTVGTU þ9oUQNQYUMKÿ
úQWXGN GV CN. üùùûC÷ 9GKTKEJ GV CN. üùù7ý. 5VTCKP %$5 û3øö KU C PCVWTCN 4CIÿ KUQNCVG
üõö -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

KP YJKEJ ITQYVJ QP INWEQUG KU UVTKEVN[ FGRGPFGPV QP TGURKTCVKQP FWG VQ C RQKPVÿ

OWVCVKQP KP VJG RAG1 IGPG þ)QHHTKPK GV CN. üùõù÷)QHHTKPK GV CN. üùùöý.
+P CFFKVKQP VQ VJG NQY CHHKPKV[ INWEQUG VTCPURQTVGTU, C JKIJ CHHKPKV[ VTCPURQTVGT
GPEQFGF D[ VJG HGT1 IGPG KU RTGUGPV KP OCP[ UVTCKPU þ$KNNCTF GV CN. üùùøý. +P EQPÿ
VTCUV VQ RAG1 CPF KHT1, YJKEJ JCXG VJG UCOG WRUVTGCO UGSWGPEGU CPF CTG KPÿ
FWEGF D[ HGTOGPVCDNG ECTDQP UQWTEGU þ9oUQNQYUMKÿúQWXGN GV CN. üùùû÷ %JGP GV CN.
üùùûD÷ <GGOCP GV CN. ûöööý, HGT1 KU GZRTGUUGF EQPUVKVWVKXGN[ þ$KNNCTF GV CN.
üùùøý. 4GIWNCVKQP QH KHT2 VTCPUETKRVKQP KU OQTG EQORNGZ. 6JG IGPG KU CEVKXG KP
IN[EGTQN, HWTVJGT KPFWEGF D[ NQY INWEQUG EQPEGPVTCVKQPU, DWV TGRTGUUGF CV JKIJ INWÿ
EQUG EQPEGPVTCVKQPU þ$TGWPKI GV CN. ûööö÷ /KNMQYUMK GV CN. ûööüý. +P NKPG YKVJ VJKU
OQFG QH TGIWNCVKQP, -JVû JCU C NQYGT -/ þ3ÿò O/ý VJCP -JVüñ4CIü þüôÿûö O/ý
þ9oUQNQYUMKÿúQWXGN GV CN. üùùû÷ /KNMQYUMK GV CN. ûööüý. $QVJ KHT1/RAG1 CPF
KHT2 CTG UWDLGEV VQ CWVQTGIWNCVKQP CU INWEQUG VTCPURQTV KU PGEGUUCT[ HQT KPFWEVKQP
D[ INWEQUG þ/KNMQYUMK GV CN. ûööüý. 6JG HCEV VJCV PQ QVJGT JGZQUG VTCPURQTVGTU DGÿ
UKFGU KHT1, KHT2, QT RAG1 CTG CDNG VQ CNNQY ITQYVJ YJGP TGURKTCVKQP KU DNQEMGF
KPFKECVGU VJCV VJGUG CTG VJG OCKP VTCPURQTVGTU VJCV ECP UWUVCKP C JKIJ IN[EQN[VKE
HNWZ. *QYGXGT, C rag1 hgt1 FQWDNG OWVCPV NKMG C kht1 kht2 hgt1 VTKRNG OWVCPV UVKNN
ITQYU QP INWEQUG þ$KNNCTF GV CN. üùùø÷ /KNMQYUMK GV CN. ûööüý KPFKECVKPI VJCV OQTG
INWEQUG VTCPURQTVGTU OKIJV DG RTGUGPV.
+V JCU DGGP TGEGPVN[ UJQYP VJCV RAG4 GPEQFGU C INWEQUG UGPUQT VJCV OC[ UKIPCN
DQVJ NQY CPF JKIJ INWEQUG EQPEGPVTCVKQPU. *GPEG, 4CIòR EQODKPGU VJG HWPEVKQPU
QH VJG 5PH3R þNQYý CPF 4IVûR þJKIJý INWEQUG UGPUQTU QH S.cerevisiae, YJKEJ DQVJ
ECP EQORNGOGPV C rag4 OWVCVKQP þ$GVKPC GV CN. ûööüý.
#RCTV HTQO NCEVQUG WRVCMG þUGG 5GEVKQP 3.û DGNQYý, NKVVNG KU MPQYP CDQWV VJG WRÿ
VCMG QH QVJGT UWICTU. 6JG -NW[XGT GHHGEV, VJCV KU VJG KPCDKNKV[ VQ ITQY CPCGTQDKECNN[
QP UWICTU VJCV ECP DG HGTOGPVGF CPF WUGF CGTQDKECNN[, JCU DGGP NKPMGF VQ CP KPCDKNÿ
KV[ VQ VCMG VJGUG UWICTU WR WPFGT CPCGTQDKQUKU. (QT K. lactis, C -NW[XGT GHHGEV JCU
DGGP TGRQTVGF HQT OCNVQUG, EGNNQDKQUG, CPF ½,½ÿVTGJCNQUG þ©PVKCP CPF $CTPGVV
üùõ3ý, UWIIGUVKPI VJCV WRVCMG U[UVGOU HQT VJGUG UWICTU OC[ GZKUV. +PFGGF, C OCNÿ
VQUG RGTOGCUG YCU TGEGPVN[ TGRQTVGF þ#.&QOKPIWG\, GV CN, WPRWDNKUJGFý. /QTGÿ
QXGT, C ICNCEVQUG RGTOGCUG PCOGF -JV3R JCU CNUQ DGGP HQWPF TGEGPVN[. 1XGTGZÿ
RTGUUKQP QH VJG EQTTGURQPFKPI IGPG HCEKNKVCVGU KPFWEVKQP QH VJG LAC IGPGU
þ%.9KGFGOWVJ CPF -.&.$TGWPKI, WPRWDNKUJGF.ý.

6.3.1.3 Upper part of glycolysis

RAG5 GPEQFGU C JGZQMKPCUG CPF KV CRRGCTU VQ DG VJG QPN[ QPG KP K. lactis. +V KU GZÿ
RTGUUGF EQPUVKVWVKXGN[ KPFGRGPFGPV QH VJG ECTDQP UQWTEG. #U GZRGEVGF HTQO VJG
RJGPQV[RG QH C S. cerevisiae UVTCKP NCEMKPI CNN VJTGG JGZQMKPCUGU, C rag5 OWVCPV
HCKNU VQ ITQY QP INWEQUG CPF HTWEVQUG CPF QP JKIJGT UWICTU VJCV RTQFWEG VJGUG
OQPQOGTU, YJGTGCU ICNCEVQUG, IN[EGTQN, CPF GVJCPQN UWRRQTV ITQYVJ. 5WTRTKUKPIN[,
C rag5 OWVCPV KU WPCDNG VQ ITQY QP NCEVQUG þ2TKQT GV CN. üùù3Dý.
+P EQPVTCUV VQ UKOKNCT OWVCPVU, K. lactis UVTCKPU YKVJ C PWNN OWVCVKQP KP VJG UKPING
RJQURJQINWEQUG KUQOGTCUG IGPG þRAG2ý ITQY YGNN QP INWEQUG þ)QHHTKPK GV CN.
üùùü÷ 5VGGPUOC CPF 6GT úKPFG ûööü÷ 1XGTMCOR GV CN. ûööûý. #NUQ, K. lactis OWÿ
VCPVU KP YJKEJ DQVJ RJQURJQHTWEVQMKPCUG IGPGU þKlPFK1, KlPFK2ý JCXG DGGP FKUÿ
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üõü

TWRVGF ECP ITQY QP INWEQUG, YJGTGCU VJG EQTTGURQPFKPI S. cerevisiae OWVCPVU ECP
PQV þ*GKPKUEJ GV CN. üùù3ý. 6JGUG FCVC UWIIGUV VJCV KP K. lactis VJG RGPVQUG RJQUÿ
RJCVG RCVJYC[ ECP D[RCUU VJGUG VYQ UVGRU QH IN[EQN[UKU. &KUTWRVKQP QH VJG IGPG HQT
VTCPUCNFQNCUG þKlTAL1ý KP VJG Klpfk1 Klpfk2 FQWDNG OWVCPV KPFGGF CDQNKUJGU
ITQYVJ þìCEQD[ GV CN. üùù3ý. 6TCPUCNFQNCUG VQIGVJGT YKVJ VTCPUMGVQNCUG GPEQFGF D[
VJG KlTKL1 IGPG þìCEQD[ CPF *GKPKUEJ üùù7ý EQPXGTVU TKDWNQUGÿôÿRJQURJCVG KPVQ
HTWEVQUGÿøÿRJQURJCVG CPF 3ÿRJQURJQIN[EGTCNFGJ[FG.
6JG HKPFKPI VJCV OWVCVKQPU KP VJG RJQURJQIN[EGTCVG IGPG, KlPGK1 þ(QWTPKGT GV
CN. üùùöý, HTQO VJG NQYGT RCTV QH IN[EQN[UKU, DNQEM ITQYVJ QP INWEQUG þ(NGGT,
SWQVGF KP ìCEQD[ GV CN. üùù3ý UWRRQTVU VJG KFGC VJCV KP K. lactis VJG RGPVQUG RJQUÿ
RJCVG RCVJYC[ ECP D[RCUU VJG HKTUV VYQ EQOOKVVGF UVGRU QH IN[EQN[UKU. 6JKU OGCPU
VJCV, KP EQPVTCUV VQ S.cerevisiae, K. lactis JCU DQVJ C UWHHKEKGPVN[ CEVKXG RGPVQUG
RJQURJCVG RCVJYC[ CPF VJG ECRCEKV[ VQ TGÿQZKFK\G VJG 0#&2* HQTOGF þ)QP\hNG\
5KUQ GV CN. üùùøý. 1Z[IGP WRVCMG GZRGTKOGPVU EQPHKTOGF VJG RTGUGPEG QH C OKVQÿ
EJQPFTKCN 0#&2* FGJ[FTQIGPCUG KP K. lactis, CP GP\[OG PQV HQWPF KP
S.cerevisiae. 6JKU GP\[OG KU QTKGPVGF VQ VJG GZVGTPCN HCEG QH VJG KPPGT OKVQEJQPÿ
FTKCN OGODTCPG CPF ECP EQWRNG VJG QZKFCVKQP QH E[VQUQNKE 0#&2* VQ VJG TGURKTCÿ
VQT[ EJCKP þ1XGTMCOR GV CN. ûööûý. 6JG KPCDKNKV[ QH VJG rag2 OWVCPV VQ ITQY KP VJG
RTGUGPEG QH CPVKO[EKP # þ)QHHTKPK GV CN. üùõùý KU PQV ECWUGF D[ CP KPCDKNKV[ VQ HQTO
GVJCPQN CU RTGXKQWUN[ TGRQTVGF þ)QHHTKPK GV CN. üùùüý, DWV D[ C TGFQZ FGHGEV. 6JG
0#&2* HQTOGF KP VJG RGPVQUG RJQURJCVG RCVJYC[ ECP PQV DG TGÿQZKFK\GF YJGP
TGURKTCVKQP KU DNQEMGF þ)QP\hNG\ 5KUQ GV CN. üùùøý.
6JG KPVGTEQPXGTUKQP QH FKJ[FTQZ[CEGVQPG RJQURJCVG CPF IN[EGTCNFGJ[FGÿ3ÿ
RJQURJCVG KU ECVCN[UGF D[ VTKQUG RJQURJCVG KUQOGTCUG GPEQFGF D[ C UKPING IGPG,
TPI1. +P EQPVTCUV VQ C UKOKNCT OWVCPV KP S.cerevisiae, C K. lactis tpi1 OWVCPV ECP
UVKNN ITQY QP INWEQUG þ%QORCIPQ GV CN. üùùùý. 6JKU FKHHGTGPEG OKIJV CICKP DG
ECWUGF D[ C OQTG RTQOKPGPV TQNG QH VJG RGPVQUG RJQURJCVG RCVJYC[ KP K. lactis,
UKPEG INWEQUG OGVCDQNK\GF XKC VJKU RCVJYC[ YKNN HQTO QPN[ VYQ VJKTFU VJG COQWPV
QH FKJ[FTQZ[CEGVQPG RJQURJCVG KP EQORCTKUQP VQ VJG FKTGEV RCVJYC[ XKC INWEQUG
KUQOGTCUG CPF RJQURJQHTWEVQMKPCUG.

6.3.1.4 Pyruvate metabolism

6JG EQPXGTUKQP QH IN[EGTCNFGJ[FGÿ3ÿRJQURJCVG VQ R[TWXCVG QEEWTU KP C PWODGT QH
UVGRU HQT YJKEJ FKHHGTGPEGU YKVJ QVJGT [GCUVU JCXG PQV DGGP TGRQTVGF. 2[TWXCVG,
JQYGXGT, KU CP KORQTVCPV DTCPEJRQKPV KP OGVCDQNKUO. ðPFGT QZ[IGPÿNKOKVGF EQPFKÿ
VKQPU 0#&* ECPPQV DG þEQORNGVGN[ý TGQZKFK\GF CPF CNEQJQNKE HGTOGPVCVKQP UVCTVU
YKVJ VJG FGECTDQZ[NCVKQP QH R[TWXCVG VQ CEGVCNFGJ[FG, YJKEJ KU HWTVJGT TGFWEGF VQ
GVJCPQN, UKOWNVCPGQWUN[ þTGýIGPGTCVKPI 0#&ï HTQO 0#&* þ(KI. 3ý.
+PCEVKXCVKQP QH VJG R[TWXCVG FGJ[FTQIGPCUG EQORNGZ D[ FKUTWRVKQP QH VJG PDA1
IGPG GPEQFKPI VJG FGECTDQZ[NCVKPI ©ü½ UWDWPKV NGCFU VQ UGXGTG ITQYVJ FGHGEVU KP
K. lactis, CNVJQWIJ ITQYVJ KU PQV EQORNGVGN[ DNQEMGF þ<GGOCP GV CN. üùùõý. 6JKU KU
FWG VQ #E%Q# UJQTVCIG UKPEG CFFKVKQP QH CP[ QH VJG COKPQ CEKFU úÿCTIKPKPG, úÿ
INWVCOCVG, úÿNGWEKPG QT úÿRTQNKPG CU PKVTQIGP UQWTEG TGUVQTGU ITQYVJ VQ YKNF V[RG
NGXGNU þ<GGOCP GV CN. üùùùý. 6JGUG COKPQ CEKFU IGPGTCVG OKVQEJQPFTKCN #E%Q#
üõû -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

0#&* 0#& +

R[TWXCVG CEGVCNFGJ[FG GVJCPQN

ü û
0#&þ2) +
3
0#&þ2)*

CEGVCVG
(KI. 3. (GTOGPVCVKQP. ü. R[TWXCVG FGECTDQZ[NCUG÷ û. CNEQJQN FGJ[FTQIGPCUG÷ 3. CNFGJ[FG
FGJ[FTQIGPCUG.

YJGP DTQMGP FQYP. +PVGTGUVKPIN[, GVJCPQN HQTOCVKQP YCU GNGXCVGF KP VJG pda1 OWÿ
VCPV. 6JKU UWIIGUVU VJGTGHQTG, VJCV KV KU VJG CEVKXKV[ QH VJG R[TWXCVG FGJ[FTQIGPCUG
EQORNGZ, URGEKHKECNN[ KVU GHHKEKGPV EQORGVKVKQP YKVJ R[TWXCVG FGECTDQZ[NCUG HQT R[ÿ
TWXCVG, YJKEJ TGPFGTU K. lactis C %TCDVTGG PGICVKXG [GCUV þUGG 5GEVKQP 3.ü.ôý.
6JG TGOCKPKPI ITQYVJ QH VJG pda1 OWVCPV KU ECWUGF D[ VJG UQÿECNNGF 2&* D[ÿ
RCUU, YJKEJ HQTOU #E%Q# D[ VJG UGSWGPVKCN CEVKXKV[ QH R[TWXCVG FGECTDQZ[NCUG
þ2FEý, CEGVCNFGJ[FG FGJ[FTQIGPCUG þ#NFý, CPF CEGV[NÿEQGP\[OG # U[PVJCUG þ#EUý.
5KPEG CV NGCUV 2FE CPF #EU CTG NQECVGF KP VJG E[VQUQN, VJG #E%Q# HQTOGF KU E[VQUQÿ
NKE. +V CRRGCTU VJCV VTCPURQTV KPVQ OKVQEJQPFTKC KU NKOKVKPI UKPEG CFFKVKQP QH UOCNN
COQWPVU QH úÿECTPKVKPG CNOQUV EQORNGVGN[ TGUVQTG ITQYVJ þ<GGOCP GV CN. üùùùý,
RTQDCDN[ D[ CEVKXCVKPI C ECTPKVKPGÿ#E%Q# UJWVVNG OGEJCPKUO þ-QJNJCY CPF 6CPÿ
9KNUQP üù77ý. 6JG CEGV[NÿITQWR KU EQWRNGF VQ ECTPKVKPG CPF VJG TGUWNVKPI CEGV[Nÿ
ECTPKVKPG KU VTCPURQTVGF QXGT VJG OGODTCPG þ$TGOGT üùõ3ý.
+P S.cerevisiae, VJG D[RCUU KU OWEJ OQTG CEVKXG. # pda1 OWVCPV ITQYU CNOQUV
CU YGNN CU C YKNF V[RG UVTCKP, CRCTV HTQO C RCTVKCN NGWEKPG FGHKEKGPE[ þ9GP\GN GV CN.
üùùûý. /QTGQXGT, VJG D[RCUU KU GXGP GUUGPVKCN UKPEG C OWVCPV YKVJ CNN VJTGG UVTWEÿ
VWTCN PDC IGPGU FGNGVGF CPF JGPEG FGXQKF QH 2FE CEVKXKV[ KU WPCDNG VQ ITQY QP
INWEQUG þ(NKMYGGTV GV CN. üùùøý. +P CFFKVKQP, KV YCU KORQUUKDNG VQ UKOWNVCPGQWUN[
FGNGVG VJG VYQ IGPGU GPEQFKPI #EU CEVKXKV[ KP S.cerevisiae, ACS1 CPF ACS2 þ8CP
FGP $GTI CPF 5VGGPUOC üùùôý. +P EQPVTCUV, C K. lactis OWVCPV NCEMKPI 2FE CEVKXKV[
ECP ITQY QP INWEQUG YKVJ VJG UCOG TCVG CU VJG YKNF V[RG UVTCKP þ$KCPEJK GV CN.
üùùøý. *QYGXGT, KV YCU UVKNN KORQUUKDNG VQ EQPUVTWEV C OWVCPV YKVJ FKUTWRVKQPU KP
DQVJ CEGV[NÿEQGP\[OG # U[PVJCUG IGPGU þ<GGOCP CPF 5VGGPUOC ûöö3ý, UWIIGUVKPI
VJCV GKVJGT #EU JCU CPQVJGT HWPEVKQP QT VJCV KP K. lactis E[VQUQNKE #E%Q# KU CNUQ
PGEGUUCT[.

6.3.1.5 Crabtree effect and fermentation

K. lactis KU IGPGTCNN[ EQPUKFGTGF CU C %TCDVTGG PGICVKXG [GCUV. +P %TCDVTGG RQUKVKXG
[GCUVU NKMG S. cerevisiae, HGTOGPVCVKQP QEEWTU KP HWNN[ CGTQDKE EQPFKVKQPU CV INWEQUG
EQPEGPVTCVKQPU GZEGGFKPI EC. ö.ûó. +P K. lactis. HGTOGPVCVKQP QPN[ UVCTVU CV TGFWEGF
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üõ3

QZ[IGP EQPEGPVTCVKQPU, C EQPFKVKQP TCRKFN[ QEEWTTKPI KP UJCMG HNCUM EWNVWTGU þ-KGTU

GV CN. üùùõý. +P CGTQDKE UJCMG HNCUM EWNVWTGU ITQYP CV JKIJ INWEQUG EQPEGPVTCVKQPU,
HQTOCVKQP QH GVJCPQN QPN[ UGVU KP CV JKIJ EGNNWNCT FGPUKVKGU YJGP QZ[IGP UWRRN[
DGEQOGU NKOKVKPI. +P EJGOQUVCV EWNVWTGU, GVJCPQN HQTOCVKQP YCU DGNQY VJG FGVGEÿ
VKQP NKOKV KP C DTQCF TCPIG QH FKNWVKQP TCVGU þ-KGTU GV CN. üùùõ÷ <GGOCP GV CN. üùùõý.
6JG %TCDVTGG GHHGEV JCU DGGP CVVTKDWVGF VQ QXGTHNQY OGVCDQNKUO CV VJG R[TWXCVG
DTCPEJRQKPV þXCP ðTM GV CN. üùõùý. *QYGXGT, VJKU ECPPQV DG VJG UQNG GZRNCPCVKQP,
UKPEG VJG CEVKXKV[ QH VJG R[TWXCVG FGJ[FTQIGPCUG EQORNGZ KU QPN[ VYKEG CU JKIJ CU
KP S. cerevisiae CPF VJG CEVKXKV[ QH R[TWXCVG FGECTDQZ[NCUG CRRTQZKOCVGN[ JCNH
þ<GGOCP GV CN. ûöööý. +P EQPVTCUV VQ S.cerevisiae, VJG PDA1 IGPG KU TGIWNCVGF CV VJG
VTCPUETKRVKQPCN NGXGN. 6JG PDA1 O40# NGXGN KU OQTG VJCP VJTGGÿHQNF JKIJGT KP
INWEQUGÿNKOKVGF EQPVKPWQWU EWNVWTGU VJCP KP IN[EGTQNÿ QT GVJCPQNÿNKOKVGF EWNVWTGU
þ<GGOCP GV CN. ûöööý. 6JKU OKIJV DG OGFKCVGF D[ VJG RAG3 IGPG RTQFWEV, VJG K.
lactis JQOQNQIWG QH PDC2 þ6K\\CPK GV CN. üùùõý.
+V JCU CNUQ DGGP RTQRQUGF VJCV UVTCKPÿURGEKHKE FKHHGTGPEGU KP VJG PWODGT CPF CEÿ
VKXKV[ QH VJG INWEQUG VTCPURQTVGTU þUGG 5GEVKQP 3.ü.ûý CTG, CV NGCUV RCTVKCNN[, TGURQPÿ
UKDNG HQT VJG V[RG QH OGVCDQNKUO, K.G. TGURKTCVQT[ QT HGTOGPVCVKXG þ$TGWPKI GV CN.
ûöööý. 5VTCKPU EQPVCKPKPI DQVJ KHT1 CPF KHT2 UJQY RTQPQWPEGF GVJCPQN RTQFWEÿ
VKQP TCVGU KP UJCMG HNCUM EWNVWTGU GXGP CV NQY EGNN FGPUKVKGU, KPFKECVKPI VJCV HGTOGPÿ
VCVKXG OGVCDQNKUO KU HCXQWTGF D[ VJG RQUUKDNG JKIJGT UWICT WRVCMG ECRCEKV[ QH UWEJ
UVTCKPU.
#U UVCVGF CDQXG, K. lactis KU %TCDVTGG PGICVKXG CPF OGVCDQNKUO KU RTGFQOKPCPVN[
TGURKTCVQT[. (GTOGPVCVKQP QPN[ UGVU KP CV NQY QZ[IGP EQPEGPVTCVKQPU þ)QP\hNG\
5KUQ GV CN. üùùø÷ -KGTU GV CN. üùùõý. 6JG HKTUV UVGR QH CNEQJQNKE HGTOGPVCVKQP KU
CEJKGXGF D[ C UKPING R[TWXCVG FGECTDQZ[NCUG IGPG KlPDCA QT KlPDC1 þ$KCPEJK
GV CN. üùùøý, YJKEJ KU CNNGNKE VQ RAG6 þ9oUQNQYUMKÿúQWXGN GV CN. üùùøý. +V KU CWVQÿ
TGIWNCVGF, KPFWEGF D[ INWEQUG CPF TGRTGUUGF D[ GVJCPQN þ&GUVTWGNNG GV CN. üùùùý.
/QTGQXGT, KV KU UVTQPIN[ KPFWEGF CV NQY QZ[IGP EQPEGPVTCVKQPU þ-KGTU GV CN. üùùõý.
&GURKVG VJG NQY KORQTVCPEG QH HGTOGPVCVKQP KP K. lactis, HQWT CNEQJQN FGJ[FTQÿ
IGPCUGU JCXG DGGP TGRQTVGF, VYQ E[VQUQNKE þKlADH1 CPF KlADH2ý CPF VYQ OKVQÿ
EJQPFTKCN þKlADH3 CPF KlADH4ý, GCEJ QH YJKEJ CNQPG ECP UWRRQTV GVJCPQN RTQÿ
FWEVKQP KP VTKRNG OWVCPVU, CNDGKV VQ FKHHGTGPV NGXGNU þ$Q\\K GV CN. üùù7 CPF
TGHGTGPEGU VJGTGKP CPF <GGOCP GV CN. ûöööý. 9JGTGCU VJG VYQ E[VQUQNKE GP\[OGU
CTG GZRTGUUGF VQ CRRTQZKOCVGN[ VJG UCOG NGXGNU QP INWEQUG, GVJCPQN, QT CEGVCVG, VJG
VYQ OKVQEJQPFTKCN KUQ\[OGU CTG GZRTGUUGF FKHHGTGPVN[. KlADH4 KU UVTQPIN[ KPÿ
FWEGF D[ GVJCPQN CPF PQV GZRTGUUGF KP ECTDQPÿNKOKVGF EQPVKPWQWU EWNVWTGU. 6JG
KlADH4 RTQOQVGT JCU GXGP DGGP RTQRQUGF CU CP KPFWUVTKCNN[ÿCRRNKECDNG, GVJCPQNÿ
KPFWEKDNG RTQOQVGT þ5CNKQNC GV CN. üùùùý. KlADH3 YCU TGRQTVGF VQ DG TGRTGUUGF D[
GVJCPQN. *QYGXGT, KP ECTDQPÿNKOKVGF EQPVKPWQWU EWNVWTGU KlADH3 YCU GZRTGUUGF
CV VJG JKIJGUV NGXGNU YKVJ GVJCPQN CU VJG ECTDQP UQWTEG CPF YJGP C INWEQUG RWNUG
YCU IKXGP VQ C INWEQUGÿNKOKVGF EQPVKPWQWU EWNVWTG VJG KlADH3 FKUCRRGCTGF TCRÿ
KFN[ CPF QPN[ TGCRRGCTGF YJGP GZEGUU INWEQUG YCU EQPUWOGF CPF GVJCPQN YCU UVKNN
RTGUGPV þ<GGOCP GV CN. ûöööý.
+P EQPVTCUV VQ OCP[ QVJGT CNEQJQN FGJ[FTQIGPCUGU, VJG OKVQEJQPFTKCN GP\[OGU
ECP WUG DQVJ 0#&* CPF 0#&2* CU EQHCEVQTU. 6JWU KlADH3 QT KlADH4 OKIJV
GPEQFG VJG GP\[OGU KORNKECVGF KP VJG TGQZKFCVKQP QH 0#&2* HQTOGF KP VJG RGPÿ
üõò -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

VQUG RJQURJCVG RCVJYC[ þ$Q\\K GV CN. üùù7÷ 1XGTMCOR GV CN. ûööûý OGPVKQPGF RTGÿ
XKQWUN[ KP VJKU EJCRVGT.
6JG RTGUGPEG QH HQWT CNEQJQN FGJ[FTQIGPCUGU KP CP QTICPKUO YKVJ C RTGFQOKÿ
PCPVN[ TGURKTCVQT[ OGVCDQNKUO OKIJV TGHNGEV VJG PGEGUUKV[ VQ EQPVTQN KPVTCEGNNWNCT
NGXGNU QH VJG JKIJN[ VQZKE CEGVCNFGJ[FG. ðPFGT NQY QZ[IGP EQPFKVKQPU, HGTOGPVCÿ
VKQP UGVU KP VQ TGNKGXG VJG TGFQZ RTQDNGO D[ TGQZKFK\KPI 0#&* þ(KI. 3ý. 1PEG VJG
GP\[OG R[TWXCVG FGECTDQZ[NCUG KU CEVKXG, UWHHKEKGPV CNEQJQN FGJ[FTQIGPCUG ECRCEÿ
KV[ UJQWNF DG RTGUGPV VQ RTGXGPV VJG DWKNF WR QH VQQ JKIJ CEGVCNFGJ[FG EQPEGPVTCÿ
VKQPU. /QTGQXGT, VJKU KFGC CNUQ TGSWKTGU VJCV CEGVCNFGJ[FG FGJ[FTQIGPCUG YJKEJ
QZKFK\GU CEGVCNFGJ[FG VQ CEGVCVG KU MGRV WPFGT EQPVTQN, UKPEG VJKU TGCEVKQP YKNN GPÿ
ITCXG VJG TGFQZ RTQDNGO D[ RTQFWEKPI 0#&þ2ý*. úKVVNG KU MPQYP CDQWV VJG
þCEGVýCNFGJ[FG FGJ[FTQIGPCUGU KP K. lactis.

6.3.1.6 Acetate and ethanol consumption

K. lactis ECP ITQY QP %ûÿECTDQP UQWTEGU. &WTKPI ITQYVJ QP GVJCPQN, CNN HQWT CNEQÿ
JQN FGJ[FTQIGPCUGU CTG VTCPUETKDGF KP ECTDQPÿNKOKVGF EQPVKPWQWU EWNVWTGU þ<GGOCP
GV CN. ûöööý, CNVJQWIJ KlADH4, GPEQFKPI VJG GVJCPQNÿKPFWEKDNG OKVQEJQPFTKCN KUQÿ
HQTO KU PQV HWNN[ GZRTGUUGF. &KUTWRVKQP QH CP[ QH VJG HQWT KUQIGPGU JCU PQ OCTMGF
GHHGEV QP VJG ITQYVJ QH VJG OWVCPV UVTCKPU QP GVJCPQN KP DCVEJ EWNVWTGU þ$Q\\K GV CN.
üùù7 CPF TGHGTGPEGU VJGTGKPý. 9JKNG KlADH3 KU TGRTGUUGF D[ GVJCPQN, CP[ QH VJG
VJTGG QVJGT CNEQJQN FGJ[FTQIGPCUGU OKIJV DG TGURQPUKDNG HQT VJG ITQYVJ QP GVJCÿ
PQN. 6JG UVTQPI KPFWEVKQP QH KlADH4 QP GVJCPQN UWIIGUVU VJCV VJKU IGPG GPEQFGU
VJG OCKP GP\[OG KP YKNF V[RG UVTCKPU.
6JG CEGVCNFGJ[FG HQTOGF KU UWDUGSWGPVN[ QZKFK\GF VQ CEGVCVG, ECVCN[\GF D[ CEÿ
GVCNFGJ[FG FGJ[FTQIGPCUG. +P S. cerevisiae CPF QVJGT QTICPKUOU, UGXGTCN 0#&ïÿ
CPF 0#&2ï ÿ FGRGPFGPV KUQHQTOU CTG MPQYP YJKEJ CTG NQECVGF KP VJG E[VQUQN QT KP
VJG OKVQEJQPFTKC þ;QUJKFC GV CN. üùùõ÷ 2TCUCF GV CN. üùùùý. 6JG PWODGT CPF NQECÿ
VKQP QH CNFGJ[FG FGJ[FTQIGPCUGU KP K. lactis KU WPMPQYP. /QUV NKMGN[, C E[VQUQNKE
KUQHQTO KU KPXQNXGF KP ITQYVJ QP GVJCPQN. ©XGP YJGP VJG OKVQEJQPFTKCN KlADH4
RTQFWEV KU VJG OCKP CNEQJQN, FGJ[FTQIGPCUG FWTKPI ITQYVJ QP GVJCPQN CPF JGPEG
CEGVCNFGJ[FG KU HQTOGF KP VJG OKVQEJQPFTKC, CEGVCNFGJ[FG ETQUUGU VJG OKVQEJQPÿ
FTKCN OGODTCPG OWEJ GCUKGT VJCP CEGVCVG, YJKEJ YQWNF TGSWKTG C URGEKCN VTCPURQTV
U[UVGO.
6JG PGZV UVGR HQT ITQYVJ QP GVJCPQN CPF ITQYVJ QP CEGVCVG TGSWKTGU CEGV[Nÿ
EQGP\[OG # U[PVJGVCUG VJCV EQPXGTVU CEGVCVG KP CEGV[N EQGP\[OG #. #U KP
S.cerevisiae, VYQ IGPGU CTG RTGUGPV YJKEJ CTG VTCPUETKDGF FKHHGTGPVN[. 9JGTGCU
KlACS1 KU TGRTGUUGF D[ INWEQUG CPF VJG VTCPUETKRV GXGP FKUCRRGCTU YKVJKP HKXG
OKPWVGU CHVGT CFFKVKQP QH C INWEQUG RWNUG VQ C INWEQUGÿNKOKVGF UVGCF[ÿUVCVG EWNVWTG,
KlACS2 O40# TGOCKPU RTGUGPV VJTQWIJQWV þ<GGOCP GV CN. ûöööý. +P GZRQPGPVKCNN[
ITQYKPI EWNVWTGU, KlACS1 KU VTCPUETKDGF CV VJG JKIJGUV NGXGN QP CEGVCVG OGFKC,
YJGTGCU KlACS2 O40# NGXGN KU JKIJGUV QP GVJCPQN þúQFK GV CN. ûööü÷ <GGOCP CPF
5VGGPUOC ûöö3ý. *QYGXGT, DQVJ VTCPUETKRVU CTG RTGUGPV QP DQVJ ECTDQP UQWTEGU CPF
OWVCPVU KP GCEJ QH VJG VYQ IGPGU ECP ITQY QP GCEJ UWDUVTCVG CNDGKV CV TGFWEGF
TCVGU þ<GGOCP CPF 5VGGPUOC ûöö3ý.
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üõô

(QT ITQYVJ QP GVJCPQN QT CEGVCVG, QZCNQCEGVCVG OWUV DG U[PVJGUK\GF VQ TGRNGPKUJ

VJG 6%# E[ENG. 6JKU QEEWTU XKC VJG IN[QZ[NCVG E[ENG XKC VYQ URGEKHKE GP\[OGU,
KUQEKVTCVG N[CUG CPF OCNCVG U[PVJCUG. /QTGQXGT, INWEQUGÿRJQURJCVGU CPF ð&2ÿ
INWEQUG CTG TGSWKTGF CU DWKNFKPI DNQEMU KP EGNN YCNN DKQIGPGUKU, UVQTCIG QH ECTDQÿ
J[FTCVGU, CPF IN[EQU[NCVKQP. 6JGUG OGVCDQNKVGU JCXG VQ DG U[PVJGUKUGF D[ INWÿ
EQPGQIGPGUKU, YJKEJ TGSWKTGU VYQ URGEKHKE GP\[OGU VJCV ECVCN[UG VJG TGXGTUG TGCEÿ
VKQPU QH VJG PQPÿTGXGTUKDNG UVGRU QH IN[EQN[UKU, HTWEVQUGÿDKUÿRJQURJCVCUG þ($2CUGý,
CPF RJQURJQÿGPQNÿECTDQZ[MKPCUG þ2%-ý. úKVVNG KU MPQYP CDQWV VJG UVTWEVWTCN K.
lactis IGPGU KPXQNXGF KP VJG IN[QZ[NCVG E[ENG CPF INWEQPGQIGPGUKU. 5QOG QH VJG
TGNGXCPV IGPGU JCXG DGGP KUQNCVGF þ<CTQT GV CN. üùù3÷ -KVCOQVQ GV CN. üùùõý, QVJGTU
CTG RTGUGPV QT RCTVKCNN[ RTGUGPV KP VJG IGPQOKE UGSWGPEGU CXCKNCDNG VQFC[ þ$QNQVKPÿ
(WMWJCTC GV CN. ûöööý. 6JGKT TGIWNCVKQP JCU DGGP UVWFKGF KP OQTG FGVCKN þUGG 5GEÿ
VKQP 3.ü.7ý.

6.3.1.7 Regulator genes

General transcription factors. 9KVJ UQOG GZEGRVKQPU FGUETKDGF DGNQY, TGIWNCVKQP
QH K. lactis OGVCDQNKUO JCU DGGP UVWFKGF KP NGUU FGVCKN VJCP KP S.cerevisiae. 9JKNG
JQOQNQIU QH IGPGTCN VTCPUETKRVKQP HCEVQTU JCXG DGGP TGRQTVGF KP K. lactis YJKEJ
ECP, #DHü þ&QTUOCP GV CN. üùùö÷ )QPECNXGU GV CN. üùùûý, QT ECPPQV, 4CRü þúCTUQP
GV CN. üùùòý, TGRNCEG VJG S. cerevisiae RTQVGKPU, TGIWNCVKQP QH VTCPUETKRVKQP CRRGCTU
VQ DG FKHHGTGPV DGVYGGP VJG VYQ URGEKGU. (QT KPUVCPEG, KP VJG RTQOQVGT QH KlQCR8,
GPEQFKPI UWDWPKV 8+++ QH VJG bcü EQORNGZ, DKPFKPI UKVGU HQT VJG VTCPUETKRVKQP HCEÿ
VQTU %DHü, #DHü, CPF VJG *CRû,3,ô EQORNGZ CTG RTGUGPV CV CRRTQZKOCVGN[ VJG UCOG
RQUKVKQP CU KP VJG RTQOQVGT QH ScKlQCR8. &GURKVG VJKU UKOKNCTKV[, TGIWNCVKQP KU FKHÿ
HGTGPV þ$TQPU GV CN. ûööüý. 5KOKNCTN[, AAC1, GPEQFKPI C OKVQEJQPFTKCN #62ñ#&2
ECTTKGT, KU RQQTN[ VTCPUETKDGF KP S. cerevisiae WPFGT CNN EQPFKVKQPU KPXGUVKICVGF.
*QYGXGT, YJGP KPVTQFWEGF KP K. lactis, KVU GZRTGUUKQP KU JKIJ þ8KQNC GV CN. üùùùý.
Sugar transport and glycolysis. RAG1 CPF KHT1, YJKEJ GPEQFG NQY CHHKPKV[ JGZÿ
QUG VTCPURQTVGTU, CTG KPFWEGF D[ INWEQUG. 5GXGTCN IGPGU CTG KPXQNXGF KP VJG TGIWNCÿ
VKQP QH INWEQUG WRVCMG KP K. lactis. 6JGUG KPENWFG RAG4 CPF RAG8, YJKEJ FKTGEVN[
CHHGEV VTCPUETKRVKQP. #U OGPVKQPGF RTGXKQWUN[, RAG4 GPEQFGU C INWEQUG UGPUQT
YJKEJ EQODKPGU VJG HWPEVKQPU QH VJG 5PH3 þNQYý CPF 4IVû þJKIJý INWEQUG UGPUQTU
QH S.cerevisiae, YJKEJ DQVJ ECP EQORNGOGPV C rag4 OWVCVKQP þ$GVKPC GV CN. ûööüý.
&KUTWRVKQP QH RAG8, GPEQFKPI C ECUGKP MKPCUG +ÿNKMG OQNGEWNG, CDQNKUJGU VTCPUETKRÿ
VKQP QH RAG1 þ%JGP GV CN. üùùû÷ $NCKUQPPGCW GV CN. üùù7ý. 6JKU KU CV NGCUV RCTVKCNN[
OGFKCVGF D[ 5EMüR, C OWNVKÿEQR[ UWRRTGUUQT QH ECUGKP MKPCUG, YJKEJ TGUVQTGU VTCPÿ
UETKRVKQP QH RAG1 KP C rag8 OWVCPV. +PVGTGUVKPIN[, KP YKNF V[RG EGNNU, QXGTRTQFWEÿ
VKQP QH 5EMü KU VQZKE, YJGTGCU C sck1 PWNN OWVCVKQP IKXGU C YGCM 4CIÿ RJGPQV[RG
CPF TGFWEGU VTCPUETKRVKQP QH RAG1 D[ øöó CU YGNN CU VTCPUETKRVKQP QH VJG RAG2,
RAG5, CPF RAG6 IGPGU þúGOCKTG GV CN. ûööûý EQFKPI HQT RJQURJQINWEQUG KUQOÿ
GTCUG, JGZQMKPCUG CPF R[TWXCVG FGECTDQZ[NCUG TGURGEVKXGN[. +V VJGTGHQTG UGGOU VJCV
5EMü KU C IGPGTCN TGIWNCVQT QH IN[EQN[UKU CPF HGTOGPVCVKQP, LWUV NKMG KVU S. cere-
visiae EQWPVGTRCTV 5IEü þ5CVQ GV CN. üùùùý. (WNN VTCPUETKRVKQP QH SCK1 FGRGPFU QP
üõø -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

KPVCEV 4CIõ. +P C rag8 OWVCPV, VJG NGXGN QH SCK1 O40# KU QPN[ òöó QH VJCV KP C
YKNF V[RG UVTCKP þúGOCKTG GV CN. ûööûý.
+P CFFKVKQP VQ FKTGEV VTCPUETKRVKQP TGIWNCVKQP D[ VJG RAG4 CPF RAG8 RTQFWEVU,
INWEQUG OGVCDQNKUO OWUV DG KPVCEV HQT HWNN KPFWEVKQP QH VJG RAG1 IGPG. /WVCVKQPU
KP VJG IGPGU HQT JGZQMKPCUG þRAG5ý CPF VJG INWEQUG VTCPURQTVGTU VJGOUGNXGU
þRAG1/KHT1/KHT2ý CDQNKUJ VTCPUETKRVKQP HTQO VJG RAG1 QT KHT1 RTQOQVGTU
þ%JGP GV CN. üùùû÷ 2TKQT GV CN. üùù3D÷ $CTKPCIC, üùùò÷ $TGWPKI GV CN. ûööö÷
/KNMQYUMK GV CN. ûööüý. #U GZRTGUUKQP QH VJG VTCPURQTVGT IGPGU VJGOUGNXGU KU UWDÿ
LGEV VQ INWEQUG KPFWEVKQP CPFñQT INWEQUG TGRTGUUKQP, C EQPVTQN EKTEWKV KU ETGCVGF VJCV
CNNQYU VJG EGNNU VQ CFLWUV INQDCN INWEQUG OGVCDQNKUO VQ VJG IN[EQN[VKE HNWZ CPF vice
versa. *GPEG INWEQUG WRVCMG KU CWVQTGIWNCVGF CPF KP UVTCKPU YKVJ DQVJ KHT1 CPF
KHT2 RTGUGPV, VJGUG IGPGU OWVWCNN[ EQPVTQN GCEJ QVJGT UWEJ VJCV VJG INWEQUG EQPÿ
EGPVTCVKQP FGVGTOKPGU VJG GZRTGUUKQP NGXGN QH GCEJ QH VJG IGPGU þ/KNMQYUMK GV CN.
ûööüý. 6JG FKHHGTGPEG YKVJ S. cerevisiae CRRGCTU VQ DG C TGUVTKEVKQP QH VJG IN[EQÿ
N[VKE HNWZ WPFGT EQPFKVKQPU QH UWHHKEKGPV QZ[IGP UWRRN[ GXGP YJGP INWEQUG KU RTGÿ
UGPV CV JKIJ EQPEGPVTCVKQPU KP VJG OGFKWO. 6JG EQPVTQN QH JGZQUG VTCPURQTVGT IGPG
TGIWNCVKQP D[ QZ[IGP JCU PQV DGGP UVWFKGF, DWV OKIJV DG QH KORQTVCPEG KP VJKU TGÿ
ICTF.
)ETü, )ETû, CPF 4CRü CTG PGEGUUCT[ HQT HWNN KPFWEVKQP QH IN[EQN[UKU KP S. cere-
visiae þðGOWTC CPF ìKICOK üùùû÷ <GPI GV CN. üùù7÷ ðGOWTC GV CN. üùù7ý. K. lactis
JQOQNQIU QH VJG IGPGU GPEQFKPI )ETü CPF 4CRü JCXG DGGP KUQNCVGF þúCTUQP GV CN.
üùùò÷ *CY GV CN. ûööüý. Kl)ETü KU CDNG VQ EQORNGOGPV VJG UNQY ITQYVJ RJGPQV[RG
QH C S. cerevisiae gcr1 OWVCPV þ*CY GV CN. ûööüý, YJKNG Kl4CRü HWPEVKQPU KP S.
cerevisiae QPN[ YJGP VJG &0# DKPFKPI FQOCKP KU TGRNCEGF D[ VJCV QH S. cerevisiae
þ)TCJCO GV CN. üùùùý. +V KU VJGTGHQTG CUUWOGF VJCV C UKOKNCT TGIWNCVKQP OGEJCPKUO
CU KP S. cerevisiae IQXGTPU IN[EQN[UKU KP K. lactis þ*CY GV CN. ûööüý.
Glucose repression. 9JGP GCUKN[ HGTOGPVCDNG UWICTU NKMG INWEQUG CTG RTGUGPV, UGXÿ
GTCN OGVCDQNKE RCVJYC[U HQT VJG WVKNK\CVKQP QH QVJGT, NGUU RTGHGTTGF ECTDQP UQWTEGU
CTG TGRTGUUGF þ)QHHTKPK GV CN. üùùôý. )NWEQUG TGRTGUUKQP KP K. lactis KU PQV CU UVTKEV
CU KP S.cerevisiae, CNVJQWIJ FKHHGTGPEGU GZKUV DGVYGGP UVTCKPU þ)QHHTKPK GV CN. üùùôý.
6JGUG FKHHGTGPEGU CTG, CV NGCUV RCTVN[, ECWUGF D[ VJG TGOCTMCDNG JGVGTQIGPGKV[ KP
JGZQUG VTCPURQTVGT IGPGU. 5VWFKGU YKVJ kht OWVCPV UVTCKPU JCXG RTQXKFGF GXKFGPEG
VJCV VJG TCVG QH INWEQUG WRVCMG JCU C UVTQPI KORCEV QP TGIWNCVKQP D[ INWEQUG
þ/KNMQYUMK GV CN. ûööü÷ 9GKTKEJ GV CN. üùù7ý. 6JG RTGUGPEG QH KHT1ÿKHT2 IGPGU
EQTTGNCVGU YKVJ C JKIJGT FGITGG QH INWEQUG TGRTGUUKQP VJCP KP RAG1 UVTCKPU. 0WNN
OWVCVKQPU KP RAG1 QT RAG5, GPEQFKPI VJG WPKSWG JGZQMKPCUG, CDQNKUJ INWEQUG TGÿ
RTGUUKQP þ2TKQT GV CN. üùù3D÷ )QHHTKPK GV CN. üùùôý, YJGTGCU OWVCVKQPU KP RAG2
JCXG PQ OCTMGF GHHGEV þ9GKTKEJ GV CN. üùù7ý.
)NWEQUG TGRTGUUKQP KP S. cerevisiae KU CEJKGXGF VJTQWIJ VJG /KIüÿ5UPøÿ6WRü
EQORNGZ þUGG %JCRVGT 3ý. *QYGXGT, YJKNG VJG NCEVQUGÿICNCEVQUG TGIWNQP QH K. lac-
tis KU KlMIG1ÿFGRGPFGPV þ&QPI CPF &KEMUQP üùù7ý, TGIWNCVKQP QH KPXGTVCUG KP VJKU
[GCUV KU PQV þ)GQTKU GV CN. üùùùý. 6JG EQORQPGPVU QH VJKU /KIüÿKPFGRGPFGPV TGRTGUÿ
UKQP OGEJCPKUO CTG WPMPQYP.
5GXGTCN IGPGU JCXG DGGP KFGPVKHKGF VJCV CTG PGEGUUCT[ HQT HWNN KPFWEVKQP QH INWÿ
EQUGÿTGRTGUUGF IGPGU CV NQY INWEQUG EQPEGPVTCVKQPU. K. lactis JQOQNQIU QH SNF1
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üõ7

CPF GAL83 YGTG KFGPVKHKGF. 6JG IGPGU FOG2 þKlSNF1ý CPF FOG1 þKlGAL83ý
YGTG KUQNCVGF D[ VJGKT CDKNKV[ VQ CHHGEV fGTOGPVCVKXG CPF oZKFCVKXG gTQYVJ þ)QHHTKPK
GV CN. üùùøý. 6JG OWVCPV RJGPQV[RG QH fog1 CPF VJG NCEM QH ETQUUÿJ[DTKFKUCVKQP
YKVJ C FOG1 RTQDG KPFKECVG VJCV QPN[ QPG QH VJG UECHHQNF RTQVGKPU KU RTGUGPV KP K.
lactis þ)QHHTKPK GV CN. üùùøý. 5KPEG KP VJGUG S. cerevisiae RTQVGKPU CRRGCT VQ EQPHGT
UWDUVTCVG URGEKHKEKV[ VQ VJG 5PHü EQORNGZ CPFñQT CTG KPXQNXGF KP VCTIGVKPI VJG
MKPCUG VQ URGEKHKE EQORCTVOGPVU, KV YKNN DG KPVGTGUVKPI VQ UGG JQY UKIPCNNKPI URGEKÿ
HKEKV[ KU CUUWTGF KP K. lactis.
$[ UWRRTGUUKQP QH C K. lactis fog2/Klsnf1 OWVCPV, VJG KlCAT8 IGPG JCU DGGP
ENQPGF. +V EQWNF EQORNGOGPV C cat8 OWVCPV KP UKPING EQR[ þ)GQTKU GV CN. ûöööý.
KLSIP4 YCU QDVCKPGF CU C OWNVKÿEQR[ UWRRTGUUQT QH C Klcat8 OWVCVKQP þì.ì. -TKLÿ
IGT, 2J& VJGUKU *CNNGý. 5WTRTKUKPIN[, FGNGVKQP QH Klcat8 FQGU PQV CHHGEV GZRTGUUKQP
QH VJG KlFBP1 CPF KlPCK1 IGPGU CPF ITQYVJ QP IN[EGTQN KU WPKORCKTGF þ)GQTKU
GV CN. ûöööý. 6JWU, KP EQPVTCUV VQ S. cerevisiae INWEQPGQIGPGUKU KP K. lactis, KV KU PQV
FGRGPFGPV QP -N%CVõ þì.ì. -TKLIGT, 2J& VJGUKU *CNNGý. *QYGXGT, -N%CVõ KU TGSWKTGF
HQT ITQYVJ QP CEGVCVG, GVJCPQN, CPF NCEVCVG UKPEG VTCPUETKRVKQP QH DQVJ KlACS IGPGU
þúQFK GV CN. ûööüý, VJG IN[QZ[NCVG E[ENG IGPGU KlICL1 þ)GQTKU GV CN. ûöööý CPF
KlMLS1 þì.ì. -TKLIGT, 2J& VJGUKU *CNNGý, CPF VJG NCEVCVG VTCPURQTVGT IGPG KlJEN1
þúQFK GV CN. ûööüý CTG TGFWEGF KP C Klcat8 OWVCPV.
#PQVJGT KORQTVCPV TGIWNCVQT[ OGEJCPKUO KU VJG *CRûñ3ñòñô EQORNGZ. +P
S.cerevisiae, VJKU EQORNGZ CEVKXCVGU IGPGU GPEQFKPI EQORQPGPVU QH VJG TGURKTCVQT[
EJCKP CPF VJG 6%# E[ENG KP VJG RTGUGPEG QH PQPÿHGTOGPVCDNG ECTDQP UQWTEGU. *Qÿ
OQNQIU QH HAP2, HAP3, CPF HAP4 JCXG DGGP KUQNCVGF HTQO K. lactis D[ JGVGTQNQÿ
IQWU EQORNGOGPVCVKQP QH VJG EQTTGURQPFKPI PWNN OWVCPVU QH S. cerevisiae þ/WNFGT
GV CN. üùùò÷ 0IW[GP GV CN. üùùô÷ $QWTICTGN GV CN. üùùùý. *QYGXGT, FKUTWRVKQP QH VJG
K. lactis IGPGU FQGU PQV NGCF VQ VJG KPCDKNKV[ VQ ITQY QP IN[EGTQN, NCEVCVG, GVJCPQN,
QT CEGVCVG KP EQORNGZ OGFKC, YJGTGCU KP OKPKOCN OGFKC Klhap2 CPF Klhap4 OWÿ
VCPVU ITGY NGUU VJCP VJG YKNF V[RG UVTCKP þúQFK GV CN. üùùõ÷ $QWTICTGN GV CN. üùùùý.
6JGUG FCVC UWIIGUV VJCV KP K. lactis TGURKTCVKQP FQGU PQV TGSWKTG VJG *CRûñ3ñòñô
EQORNGZ.
+PFGGF, VTCPUETKRVKQP QH KlCYC1, GPEQFKPI E[VQEJTQOG c, KU PQV CHHGEVGF KP C
Klhap3 OWVCPV, FGURKVG VJG RTGUGPEG QH C DKPFKPI UKVG HQT VJG *CR EQORNGZ KP VJG
KlCYC1 RTQOQVGT þ(TGKTGÿ2KEQU GV CN. üùù3÷ /WNFGT GV CN. üùùò÷ (TGKTGÿ2KEQU GV CN.
üùùô÷ 4COKN GV CN. üùùõý. 6JG TGURKTCVQT[ IGPGU KlCYC1, KlQCR7, CPF KlQCR8,
VJG NCVVGT VYQ GPEQFG UWDWPKVU QH VJG bcü EQORNGZ, CTG PQV TGRTGUUGF D[ INWEQUG KP
VJG RTGUGPEG QH C PQPÿHGTOGPVCDNG ECTDQP UQWTEG þ/WNFGT GV CN. üùùôCý CNVJQWIJ
KlCYC1 O40# KU CDUGPV HTQO EGNNU ITQYP KP ô ó INWEQUG þ/WNFGT GV CN. üùùòý
CPF ECTDQP ECVCDQNKVG, TGRTGUUKQP QH VJG IGPG JCU DGGP TGRQTVGF HQT CPQVJGT UVTCKP
þ(TGKTGÿ2KEQU GV CN. üùùôý.
Respiration and fermentation. /KETQCTTC[ FCVC JCXG UJQYP VJCV KP S. cerevisiae
VTCPUETKRVKQP QH QXGT 3öö IGPGU KU CHHGEVGF D[ VJG RTGUGPEG QT CDUGPEG QH OQNGEWNCT
QZ[IGP þ6GT úKPFG GV CN. üùùùý. 4GRTGUUKQP CPF CEVKXCVKQP QH UQÿECNNGF J[RQZKE QT
CPCGTQDKE IGPGU KU OGFKCVGF D[ JGOG, VJG 5UPøÿ6WRü EQORNGZ CPF UGXGTCN TGIWNCÿ
VQTU, KPENWFKPI HAP1, ROX1, UPC2, MOX1 CPF MOX2 þ6GT úKPFG CPF 5VGGPUOC
ûöö3ý. *QOQNQIU QH VJGUG IGPGU JCXG PQV DGGP KFGPVKHKGF UQ HCT KP K. lactis. #Nÿ
üõõ -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

VJQWIJ K. lactis ECPPQV UWUVCKP ITQYVJ KP VJG EQORNGVG CDUGPEG QH OQNGEWNCT QZ[ÿ
IGP, KV TGCEVU VQ NQY QZ[IGP EQPEGPVTCVKQPU. KlHEM1 CPF KlHEM13 GPEQFKPI VJG
HKTUV CPF UKZVJ UVGR KP JGOG DKQU[PVJGUKU, TGURGEVKXGN[, KPETGCUG VTCPUETKRVKQP WPFGT
J[RQZKE EQPFKVKQPU. +PVGTGUVKPIN[, KlHEM13 þ)QP\hNG\ÿ&QOKPIWG\ GV CN. ûöööý
CPF VQ C NQYGT GZVGPV KlHEM1 þ)QP\hNG\ÿ&QOKPIWG\ GV CN. üùù7ý CTG TGRTGUUGF D[
JGOG, VJWU ETGCVKPI CP CWVQTGIWNCVQT[ NQQR. KlCYC1 CPF VJG E[VQEJTQOG cü IGPG
KlCYT1 þ)DGNUMC GV CN. üùùøý, CTG VKIJVN[ EQPVTQNNGF D[ QZ[IGP CPF JGOG, YJKNG
VYQ QVJGT TGURKTCVQT[ IGPGU, KlQCR7 CPF KlQCR8, CTG QPN[ OQFGTCVGN[ JKIJGT
GZRTGUUGF KP JGOGÿUWHHKEKGPV QT PQTOQZKE EQPFKVKQPU þ)QP\hNG\ÿ&QOKPIWG\ GV CN.
ûöööý.
#V NQYÿQZ[IGP EQPEGPVTCVKQPU, HGTOGPVCVKQP UGVU KP, DWV JQY VJKU KU TGIWNCVGF KU
PQV ENGCT. 6JG HKTUV UVGR KP VJG HGTOGPVCVKQPÿURGEKHKE RCVJYC[ KU RGTHQTOGF D[ R[ÿ
TWXCVG FGECTDQZ[NCUG, YJKEJ KP K. lactis KU GPEQFGF D[ C UKPING IGPG þ$KCPEJK GV CN.
üùùøý. #U FGUETKDGF RTGXKQWUN[ þUGG 3.ü.ôý VTCPUETKRVKQP TGIWNCVKQP QH VJG IGPG KU
EQORNGZ. +V KU CWVQTGIWNCVGF, KPFWEGF D[ INWEQUG CPF NQY QZ[IGP EQPEGPVTCVKQPU
CPF TGRTGUUGF D[ GVJCPQN. )NWEQUG KPFWEVKQP QH VJG IGPG TGSWKTGU KPVCEV IN[EQN[UKU
UKPEG OWVCVKQPU KP INWEQUG WRVCMG þRAG1ý, JGZQMKPCUG þRAG5ý, CPF INWEQUG KUQOÿ
GTCUG þRAG2ý CU YGNN CU KP TGIWNCVQTU QH VJGUG IGPGU þRAG8, KlGGS1, SCK1ý CDQNÿ
KUJ QT TGFWEG VTCPUETKRVKQP KP INWEQUG OGFKC þúW[VGP GV CN. üùù3÷ $KCPEJK GV CN.
üùùø÷ úGOCKTG GV CN. ûööûý..
# PWNN OWVCVKQP KP RAG3, VJG JQOQNQI QH VJG PDC2 IGPG þ2TKQT GV CN. üùùøý
UVTQPIN[ TGFWEGU VTCPUETKRVKQP QH KlPDC1, CPF KlTHI4 CPF KlTHI5, VYQ IGPGU KPÿ
XQNXGF KP VJKCOKPG DKQU[PVJGUKU 6JKCOKPGR[TQRJQURJCVG þ622ý KU C EQHCEVQT QH
UGXGTCN GP\[OGU, KPENWFKPI R[TWXCVG FGECTDQZ[NCUG CPF VJG ©ü! UWDWPKV QH VJG R[ÿ
TWXCVG FGJ[FTQIGPCUG EQORNGZ. 6TCPUETKRVKQP QH KlPDA1, GPEQFKPI VJG NCVVGT, KU
RCTVN[ TGRTGUUGF D[ 4CI3 þ6K\\CPK GV CN. üùùõý. 6JGUG FCVC RQKPV VQ C TQNG QH 4CI3
KP VJG QPUGV QH HGTOGPVCVKQP D[ CEVKXCVKPI R[TWXCVG FGECTDQZ[NCUG CPF TGFWEKPI
R[TWXCVG FGJ[FTQIGPCUG CEVKXKV[ þ6K\\CPK GV CN. üùùõý.

6.3.2 LCEVQUG WVKNK\CVKQP

6JG CDKNKV[ VQ WVKNKUG NCEVQUG CU C ECTDQP UQWTEG KU TCTG COQPI [GCUVU. 6JG IGPGVKEU
CPF RJ[UKQNQI[ QH NCEVQUG OGVCDQNKUO KP K. lactis JCU VJGTGHQTG DGGP UVWFKGF GZÿ
VGPUKXGN[. &GITCFCVKQP QH NCEVQUG KP OKNM HQT NCEVQUGÿKPVQNGTCPV JWOCPU DGNQPIGF
VQ VJG GCTN[ CRRNKECVKQPU QH K. lactis KP DKQVGEJPQNQI[. 9JG[ KU C NCEVQUGÿTKEJ
YCUVG RTQFWEV QH FCKT[ KPFWUVT[ YJKEJ KU WUGF CU C ECTDQP UQWTEG KP K. lactisÿ
OGFKCVGF DKQEQPXGTUKQP RTQEGUUGU þ)JCN[ GV CN. üùù3÷ /CWNNW GV CN. üùùùý.
úCEVQUG KU VCMGP WR D[ C URGEKHKE RGTOGCUG CPF J[FTQN[UGF KPVTCEGNNWNCTN[ D[ C
"ÿICNCEVQUKFCUG KPVQ INWEQUG CPF ICNCEVQUG þ4KNG[ GV CN. üùõ7 CPF TGHGTGPEGU
VJGTGKPý. úCEVQUG OGVCDQNKUO KU KPFWEKDNG D[ NCEVQUG QT ICNCEVQUG KP VJG OGFKWO.
+PFWEVKQP D[ NCEVQUG TGSWKTGU UWICT WRVCMG CPF J[FTQN[UKU UKPEG KPVTCEGNNWNCT ICNCEÿ
VQUG UGTXGU CU VJG KPFWEKPI OQNGEWNG þUGG DGNQYý. )CNCEVQUG KU OGVCDQNKUGF D[ VJG
GP\[OGU QH VJG úGNQKT RCVJYC[, GPEQFGF D[ VJG IGPGU GAL1, GAL10, CPF GAL7,
YJKEJ CTG EQÿTGIWNCVGF YKVJ VJG ¾ÿICNCEVQUKFCUG CPF NCEVQUG RGTOGCUG IGPGU LAC4
CPF LAC12 IGPGU þ4KNG[ CPF &KEMUQP, üùõòý.
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üõù

#P WPWUWCNN[ NCTIG û.ø MD FKXGTIGPV EQPVTQN TGIKQP UGRCTCVGU LAC4 CPF LAC12
CPF DKPFU TGIWNCVQT[ RTQVGKPU YJKEJ EQÿQTFKPCVGN[ EQPVTQN GZRTGUUKQP QH DQVJ
IGPGU D[ EQORNGZ RTQVGKPÿRTQVGKP KPVGTCEVKQPU þúGQPCTFQ GV CN. üùõ7÷ ){FGEMG GV
CN. üùùü÷ -TKLIGT CPF $TGWPKI, WPRWDNKUJGF FCVCý. 6JG TGIWNCVQT TGURQPUKDNG HQT
VTCPUETKRVKQP CEVKXCVKQP KP TGURQPUG VQ ICNCEVQUG YCU UJQYP VQ DG VJG JQOQNQI QH
)CNò, PCOGF úCEù QT -N)CNò þ4W\\K GV CN. üùõ7÷ 5CNOGTQP CPF ìQJPUVQP, üùõø÷
9TC[ GV CN. üùõ7÷ $TGWPKI CPF -WIGT, üùõ7ý CPF HWTVJGT TGUGCTEJ KPVQ VJG TGIWNCÿ
VKQP QH VJG K. lactis LAC/GAL TGIWNQP D[ VJKU OQNGEWNG ITGCVN[ DGPGHKVGF HTQO VJG
UKOKNCTKV[ VQ VJG S. cerevisiae U[UVGO þEQOR. 4GGEG CPF 2NCVV, üùù7÷ 5EJCHHTCVJ CPF
$TGWPKI, ûööö HQT TGEGPV TGXKGYUý.
&GURKVG VJG HCEV VJCV Klgal4 OWVCPV ECP DG EQORNGOGPVGF D[ VJG S. cerevisiae
GAL4 IGPG CPF vice versa þ4KNG[ GV CN. üùõ7÷ 5CNOGTQP CPF ìQJPUVQP, üùõøý, VJGTG
KU C TGOCTMCDNG FGITGG QH URGEKGU URGEKHKEKV[ KP VJG VTCPUETKRVKQPCN UYKVEJ VJCV TGIWÿ
NCVGU LAC/GAL IGPG GZRTGUUKQP. #EVWCNN[, VJG NCEM QH TGFWPFCPE[ KP VJG K. lactis
IGPQOG RTQXKFGF C ENWG CU VQ JQY )CNò HWPEVKQP KU CEVKXCVGF KP TGURQPUG VQ ICNCEÿ
VQUG þ/G[GT GV CN. üùùü÷ <GPMG GV CN. üùùøý. +P EQPVTCUV VQ S. cerevisiae, K. lactis
UVTCKPU FGNGVGF HQT VJG KlGAL1 IGPG GPEQFKPI ICNCEVQMKPCUG CTG WPCDNG VQ CEVKXCVG
VTCPUETKRVKQP KP TGURQPUG VQ NCEVQUG QT ICNCEVQUG. *QYGXGT, Klgal1 OWVCPV CNNGNGU
NCEMKPI ICNCEVQMKPCUG CEVKXKV[ GZKUV VJCV TGVCKP VJG TGIWNCVQT[ HWPEVKQP TGURQPFKPI
VQ ICNCEVQUG. -N)CNü KU VJWU C DKHWPEVKQPCN RTQVGKP YKVJ GP\[OCVKE CPF TGIWNCVQT[
CEVKXKV[ YJGTGCU S. cerevisiae JCU VYQ RTQVGKPU. 6JG TGIWNCVQT[ HWPEVKQP KU GSWKXCÿ
NGPV VQ VJCV RTQXKFGF D[ VJG S. cerevisiae GAL3 IGPG RTQFWEV, C ENQUG JQOQNQI QH
ICNCEVQMKPCUG VJCV JCU NQUV VJG GP\[OCVKE CEVKXKV[ þ/G[GT GV CN. üùùü÷ 2NCVV GV CN.
ûöööý.
)GPG UJWVVNG GZRGTKOGPVU DGVYGGP S. cerevisiae CPF K. lactis JCXG UJQYP VJCV
VJG TGIWNCVQT[ HWPEVKQP QH GAL1 CPF GAL3 EQPUKUVU QH KVU URGEKHKE DKPFKPI VQ
)CNõö, YJKEJ DKPFU VQ C TGIKQP QXGTNCRRKPI VJG CEVKXCVKQP FQOCKP QH )CNò VJGTGD[
DNQEMKPI VJG CEVKXCVKQP HWPEVKQP. )CNõöÿOGFKCVGF KPJKDKVKQP KU TGNKGXGF D[ FKTGEV
)CNõöÿ)CNüñ)CN3 KPVGTCEVKQP, YJKEJ TGSWKTGU ICNCEVQUG CPF #62. )CN3 QPN[
YGCMN[ KPVGTCEVU YKVJ -N)CNõö CPF ECP PQV EQPHGT KPFWEVKQP KP K. lactis WPNGUU VJG
KlGAL80 IGPG KU TGRNCEGF D[ ScGAL80 þ<GPMG GV CN. üùùøý.
)KXGP VJG JKIJ UGSWGPEG UKOKNCTKV[ DGVYGGP )CNüñ)CN3 þ$CLYC GV CN. üùõõ÷ 2NCVV
GV CN. ûöööý CU YGNN CU DGVYGGP VJG )CNõö RTQVGKPU HTQO DQVJ [GCUVU þ<GPMG GV CN.
üùù3ý VJG URGEKHKEKV[ QH VJG KPVGTCEVKQP KU UWTRTKUKPI. 2QUUKDN[, FKHHGTGPEGU GZKUV KP
VJG OGEJCPKUO QH TGNKGXKPI 5E)CNõöñ-N)CNõö KPJKDKVKQP D[ KPVGTCEVKQP YKVJ
)CN3ñ-N)CNü. 5E)CNõö JCU DGGP UJQYP VQ UJWVVNG DGVYGGP VJG PWENGWU CPF VJG E[ÿ
VQRNCUO KP S. cerevisiae YJGTGCU -N)CNõö UGGOU VQ DG C PWENGCT RTQVGKP þ2GPI CPF
*QRRGT ûööö÷ -CRR GV CN, KP RTGRCTCVKQPý. /QTGQXGT, ECTDQP UQWTEG TGIWNCVGF
RJQURJQT[NCVKQP QH -N)CNõö EQPVTKDWVGU VQ VJG TGIWNCVKQP QH VJG UYKVEJ YJKNG VJGTG
KU PQ RJQURJQT[NCVKQP QH 5E)CNõö þ<GPMG GV CN. üùùùý. %QPXGTUGN[, VJG RJQURJQT[ÿ
NCVKQP UKVG 5GTÿøùù QH 5E)CNò YJKEJ EQPVTKDWVGU VQ TGIWNCVKQP KP S. cerevisiae
þ5CFQYUMK GV CN. üùùøý KU PQV EQPUGTXGF KP -N)CNò. 6JG EQPEGPVTCVKQP QH )CNò
RNC[U CP KORQTVCPV TQNG KP VJG TGIWNCVKQP QH VJG TGIWNQP CPF VTCPUETKRVKQPCN TGIWNCÿ
VKQP QH VJG GAL4 IGPGU FKHHGTU DGVYGGP S. cerevisiae CPF K. lactis KP VJCV KlGAL4
KU UWDLGEV VQ CWVQTGIWNCVKQP þ<CEJCTKCG CPF $TGWPKI üùù3÷ %\[\ GV CN. üùù3ý.
üùö -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

úCEVQUG CU QRRQUGF VQ ICNCEVQUG KU CP CDWPFCPV UWICT KP VJG PCVWTCN JCDKVCV QH K.

lactis, YJKEJ OC[ GZRNCKP YJ[ S. cerevisiae CPF K. lactis JCXG FKXGTIGF KP VJG
TGIWNCVKQP QH VJG LAC/GAL TGIWNQP. 5KPEG KPVTCEGNNWNCT ICNCEVQUG KU VJG KPFWEGT,
VJG TGIWNCVKQP QH UWICT WRVCMG RNC[U CP KORQTVCPV TQNG KP VTCPUETKRVKQPCN EQPVTQN QH
LAC/GAL IGPG GZRTGUUKQP. úCEVQUG WRVCMG D[ VJG NCEVQUG RGTOGCUG QEEWTU D[ RTQÿ
VQP U[ORQTV, YJKEJ CNNQYU HQT KPVTCEGNNWNCT CEEWOWNCVKQP QH VJG UWICT þ&KEMUQP
CPF $CTT üùõ3ý. )CNCEVQUG ECP DG VTCPURQTVGF D[ VJG UCOG RGTOGCUG DWV, KP CFFKÿ
VKQP, QVJGT VTCPURQTVGTU DGNQPIKPI VQ VJG JGZQUG VTCPURQTVGT UWDHCOKN[ QH OCLQT HCÿ
EKNKVCVQTU ECP OGFKCVG ICNCEVQUG WRVCMG FQYP C EQPEGPVTCVKQP ITCFKGPV. 6JG JGZQUG
VTCPURQTVGT 4CIü KU KPFWEGF D[ XCTKQWU JGZQUGU KPENWFKPI ICNCEVQUG CPF OC[ DG
QPG QH VJGUG þ2TKQT GV CN. üùù3Dý. +P CFFKVKQP, CU OGPVKQPGF CDQXG, C PGY ICNCEVQUG
CPF INWEQUG VTCPURQTVGT IGPG, KHT3, JCU TGEGPVN[ DGGP ENQPGF. 5KPEG VJG LAC12
IGPG KU GZRTGUUGF CV C XGT[ NQY TCVG KP PQPÿKPFWEGF EGNNU þ){FGEMG GV CN. üùùüý,
VJGUG QVJGT VTCPURQTVGTU OC[ RNC[ CP KORQTVCPV TQNG KP VJG KPKVKCVKQP QH KPFWEVKQP.
6JG IGPGU LAC4 CPF LAC12 JCXG DGGP VTCPUHGTTGF VQ S. cerevisiae CPF YGTG
UJQYP VQ DG UWHHKEKGPV VQ CNNQY HQT ITQYVJ QP NCEVQUG þ4WDKQÿ6GZGKTC GV CN. ûööüý.
*QYGXGT, OQUV S. cerevisiae VTCPUHQTOCPVU UJQYGF UNQY ITQYVJ TCVGU CPF RQQT
GZRTGUUKQP QH VJG LAC IGPGU þ5TGGMTKUJPC CPF &KEMUQP üùõôý CPF VJG HGY VTCPUÿ
HQTOCPVU VJCV ITGY HCUVGT EQPVCKPGF OWNVKRNG KPVGITCVGF EQRKGU QH LAC4-LAC12
IGPGU. 5KPEG 5E)CNòR ECP CEVKXCVG VJG LAC IGPGU KP K. lactis, VJG RQQT GZRTGUUKQP
QH K. lactis LAC IGPGU KP S. cerevisiae KU RTQDCDN[ FWG VQ OGEJCPKUOU VJCV TGUVTKEV
CEEGUU QH )CNòR VQ VJG DKPFKPI UKVGU KP VJG LAC4-LAC12 RTQOQVGT þúCPIJCOOGT
CPF $TGWPKI, WPRWDNKUJGFý.

6.3.3 ÿJG RGVKVGýPGICVKXG RJGPQV[RG

/GVCDQNKUO QH K. lactis KU RTGFQOKPCPVN[ TGURKTCVQT[ CPF VJG SWGUVKQP KU YJGVJGT

VJKU [GCUV ECP ITQY KP VJG EQORNGVG CDUGPEG QH QZ[IGP. 9JGTGCU, KV KU IGPGTCNN[
CEEGRVGF VJCV K. lactis FQGU PQV ITQY WPFGT UVTKEV CPCGTQDKE EQPFKVKQPU þ5WDsM GV
CN. üù7ò÷ 8KUUGT GV CN. üùùö÷ 6To\oIWGV GV CN. üùùùý, QVJGTU JCXG TGRQTVGF ITQYVJ
þ©PVKCP CPF $CTPGVV üùõ3ý QT GXGP CDWPFCPV ITQYVJ þ)QP\hNG\ 5KUQ GV CN. üùùøý
WPFGT UWEJ EQPFKVKQPU.
&GURKVG VJKU EQPVTQXGTU[, KV JCU DGGP HKTON[ GUVCDNKUJGF VJCV K. lactis KU ÉRGVKVGÿ
PGICVKXGÌ. +P S. cerevisiae UOCNN EQNQPKGU, RGVKVGU, CU QRRQUGF VQ ITCPFGU, CRRGCT
URQPVCPGQWUN[ FWG VQ NCTIG FGNGVKQPU KP QT GXGP EQORNGVG NQUU QH VJG OKVQEJQPFTKCN
IGPQOG. %QPUGSWGPVN[, TGURKTCVKQP KU NQUV CPF RGVKVGU ECPPQV ITQY QP PQPÿ
HGTOGPVCDNG ECTDQP UQWTEGU. 6JG HTGSWGPE[ QH RGVKVGU ECP DG TCKUGF UKIPKHKECPVN[
D[ GZRQUWTG QH VJG EGNNU VQ KPVGTECNCVKPI CIGPVU UWEJ CU GVJKFKWO DTQOKFG. ©XGP VJG
WUG QH UWEJ CIGPVU FQGU PQV NGCF VQ VJG CRRGCTCPEG QH UVCDNG RGVKVGU KP K. lactis.
6JKU KU UQOGYJCV UWTRTKUKPI UKPEG VJKU [GCUV KU CDNG VQ HGTOGPV CPF RTQFWEG GVJCPQN
CPF VJG 4CIï UVTCKPU ECP ITQY KP VJG CDUGPEG QH TGURKTCVKQP YJGP VJKU KU DNQEMGF D[
CPVKO[EKP # þ9oUQNQYUMKÿúQWXGN GV CN. üùùûCý QT DNQEMGF D[ FGNGVKQP QH VJG
WPKSWG KlCYC1 IGPG þ%JGP CPF %NCTMÿ9CNMGT üùù3ý.
*QYGXGT, OWVCVKQPU KP GKVJGT VJG ½, ¾, QT Ä UWDWPKVU QH VJG (ü UWDWPKV QH VJG OKÿ
VQEJQPFTKCN (ö(üÿ#62 U[PVJCUG OC[ ECWUG C RGVKVGÿRQUKVKXG RJGPQV[RG. ðRQP
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üùü

VTGCVOGPV YKVJ GVJKFKWO DTQOKFG, CP[ QH VJGUG OWVCPVU TGCFKN[ HQTOU Ðö RGVKVGU.
*QY VJGUG OWVCVKQPU UWRRTGUU Ðö NGVJCNKV[ KU WPENGCT. 6JG (ö UWDWPKV FQGU PQV CRÿ
RGCT VQ RNC[ C TQNG CPF VJG CDGTTCPV (ü UWDWPKV ECP UVKNN DG HQTOGF KP VJG CDUGPEG QH
(ö þ%JGP GV CN. üùùõ CPF TGHGTGPEGU VJGTGKPý. 6JG OWVCPVU CTG TGURKTCVQT[ EQORGÿ
VGPV, DWV NQUG VJKU CDKNKV[ KP VJG RTGUGPEG QH CP QVJGTYKUG ET[RVKE OWVCVKQP þNKR$ÿüý
KP VJG LIPB IGPG, GPEQFKPI C NKRQ[NÿRTQVGKP NKICUG KPXQNXGF KP VJG NKRQ[NCVKQP QH
RTQVGKPU þ%JGP üùù7ý.
+P S.cerevisiae, VYQ IGPGU CTG MPQYP YJKEJ CTG TGSWKTGF HQT VJG RGVKVGÿRQUKVKXG
RJGPQV[RG, K.G. OP1/AAC2 QPG QH VJTGG OKVQEJQPFTKCN #62ñ#&2 VTCPUNQECVQT
IGPGU CPF PEL1/PGS1 GPEQFKPI RJQURJCVKF[NIN[EGTQNRJQURJCVG U[PVJCUG KPÿ
XQNXGF KP ECTFKQNKRKP DKQU[PVJGUKU. $QVJ op1/aac2 CPF pel1/pgs1 OWVCVKQPU TGPFGT
S. cerevisiae RGVKVGÿPGICVKXG þ)DGNUMC GV CN. üùùùý. +P EQPVTCUV VQ S.cerevisiae, K.
lactis JCU C UKPING OKVQEJQPFTKCN #62ñ#&2 VTCPUNQECVQT þ8KQNC GV CN. üùùôý CPF
FKUTWRVKQP QH VJG IGPG OCMGU VJG OWVCPVU TGURKTCVQT[ FGHKEKGPV CPF ECWUGU CP KPÿ
CDKNKV[ VQ ITQY QP ICNCEVQUG, OCNVQUG, QT TCHHKPQUG. 6JG OWVCPV EQWNF DG HWNN[
EQORNGOGPVGF D[ GKVJGT ScAAC1 QT ScAAC2 þ8KQNC GV CN. üùùùý. +V YQWNF DG KPVGTÿ
GUVKPI VQ UGG YJGVJGT VJG EQORNGOGPVGF UVTCKPU CTG UVKNN RGVKVGÿPGICVKXG. 5KOKNCTN[,
VJG KlPEL1/PGS1 IGPG JCU TGEGPVN[ DGGP KUQNCVGF, DWV HWTVJGT TGUGCTEJ CYCKVU VJG
KUQNCVKQP QH C OWVCPV þ5.6[EKCMQXC GV CN. WPRWDNKUJGFý.

6.3.4 -KNNGT 5VTCKPU

#U OGPVKQPGF KP UGEVKQP ø.û.û.û, OCP[ K. lactis UVTCKPU EQPVCKP NKPGCT RNCUOKFU VJCV
GPEQFG C MKNNGT VQZKP. 6JGUG UVTCKPU CTG CDNG VQ UWRRTGUU VJG ITQYVJ QH EQORGVKPI
[GCUVU D[ VJG CEVKXKV[ QH VJG UGETGVGF MKNNGT VQZKP QT \[OQEKP. 6JGUG UVTCKPU CTG RTQÿ
VGEVGF CICKPUV VJG VQZKP D[ CP KOOWPKV[ FGVGTOKPCPV NQECVGF QP Mü CPF RQUUKDN[
UQOG HWPEVKQP QH Mû. 6JG OGEJCPKUOU QH KOOWPKV[ CESWKUKVKQP CTG EQORNGVGN[ WPÿ
MPQYP. 4GUGCTEJ KP UGXGTCN NCDU JCU HQEWUUGF QP OGEJCPKUOU VJCV TGPFGT [GCUVU
UGPUKVKXG VQ VJG VQZKP CPF QP VJG KPVTCEGNNWNCT VQZKP VCTIGVU. 6JG TGUWNVU UWIIGUV VJCV
VJG OQFG QH CEVKQP QH K. lactis MKNNGT VQZKP TGRTGUGPVU C PQXGNV[ COQPI OKETQDKCN
VQZKPU.
5GPUKVKXG [GCUV IGPGTC KPENWFG Saccharomyces, Kluyveromyces CPF Candida
DWV PQV Schizosaccharomyces þ)WPIG GV CN. üùõü÷)WPIG CPF 5CMCIWEJK, üùõüý. S.
cerevisiae OWVCPVU YKVJ TGFWEGF EJKVKP EQPVGPV KP VJG EGNN YCNN CTG RCTVKCNN[ QT GPÿ
VKTGN[ TGUKUVCPV CICKPUV VJG VTKOGTKE GZQVQZKP KPFKECVKPI VJCV EJKVKP HWPEVKQPU CU C
FQEMKPI UKVG QT TGEGRVQT þìCDNQPQYUMK GV CN. ûööüý. +PFGGF, CNN VJTGG UWDWPKVU QH VJG
GZQVQZKP ECP DG DQWPF VQ CP KOOQDKNK\GF EJKVKPÿOCVTKZ. 5KPEG VJG ½ÿUWDWPKV
UJQYU UGSWGPEG UKOKNCTKV[ VQ EJKVKPCUGU, VJG RQUUKDKNKV[ GZKUVU VJCV EJKVKP FGITCFCÿ
VKQP KU TGSWKTGF HQT VQZKP GPVT[ KPVQ VCTIGV EGNNU. +PVTCEGNNWNCT GZRTGUUKQP QH VJG Äÿ
UWDWPKV TGUWNVU KP C ITQYVJ CTTGUV þ$WVNGT GV CN. üùùüDý. 6JGTGHQTG, CV NGCUV VJG Äÿ
UWDWPKV KU NKMGN[ VQ GPVGT VJG VCTIGV EGNN. S. cerevisiae GZRTGUUKPI VJKU ÄÿUWDWPKV
EQPFKVKQPCNN[ WPFGT VJG EQPVTQN QH KPFWEKDNG RTQOQVGTU UGTXGF VQ KFGPVKH[ KPVTCEGNÿ
NWNCT VQZKP VCTIGVU þ616Uý. 1H VJG VQZKPÿTGUKUVCPV OWVCPVU KFGPVKHKGF KP VTCPURQUQP
OWVCIGPGUKU UETGGPU C OCLQTKV[ KU FGHGEVKXG KP VJG ©NQPICVQT EQORNGZ þ(GNNQYU GV
CN. ûööö÷ (TQJNQHH GV CN. ûöö3ý C UKZ UWDWPKV EQORNGZ RWTKHKGF HTQO 40# RQN[ÿ
üùû -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

OGTCUG UVCDN[ CUUQEKCVGF YKVJ EJTQOCVKP þ1VGTQ GV CN. üùùù÷ 9KPMNGT GV CN. ûööüý.
&GNGVKQPU QH GCEJ QH VJG UKZ UWDWPKVU EQPHGTTGF C VQZKPÿTGUKUVCPV RJGPQV[RG CPF CPÿ
QVJGT VQZ4 OWVCPV, kti12, YCU UJQYP VQ FGHKPG CP CFFKVKQPCN EQORQPGPV CV NGCUV
VTCPUKGPVN[ CUUQEKCVGF YKVJ VJG EQORNGZ þ(KEJVPGT GV CN. ûööûý. 1PG QH VJG UWDWPKVU
GPEQFGF D[ ELB3/TOT3 JCU JKUVQPG VTCPUHGTCUG CEVKXKV[ VJCV KU GUUGPVKCN VQ EQPHGT
UGPUKVKXKV[ VQ ÄÿVQZKP. 9JGVJGT QT PQV ÄÿVQZKP DKPFU FKTGEVN[ VQ ©NQPICVQT QT TGÿ
SWKTGU ©NQPICVQT HWPEVKQP HQT ITQYVJ JCU PQV DGGP UQNXGF UQ HCT. ©NQPICVQT YCU
UJQYP VQ DG KPXQNXGF KP VTCPUETKRVKQP GNQPICVKQP CPF &0# TGRCKT þ5XGLUVTWR ûööûý
CNVJQWIJ KV FQGU PQV CRRGCT VQ DG CUUQEKCVGF YKVJ VJG OCLQTKV[ QH GNQPICVKPI RQN[ÿ
OGTCUG.

6.4. +PFWUVTKCN CRRNKECVKQPU

+PFWUVTKCN KPVGTGUV HQT VJG WVKNK\CVKQP QH K.lactis UVGOU HTQO þKý VJG %TCDVTGG PGICÿ
VKXG EJCTCEVGT þUGG CDQXGý, þKKý VJG HCEV VJCV HGTOGPVCVKQP VGEJPQNQI[ KU GUVCDNKUJGF
HQT K. lactis UKPEG GP\[OGU, RCTVKEWNCTN[ NCEVCUG þ¾ÿICNCEVQUKFCUGý YGTG RWTKHKGF
HTQO VJKU QTICPKUO QP C NCTIG UECNG, þKKKý PWOGTQWU RWDNKECVKQPU CPF RCVGPVU TGRQTVÿ
KPI VJCV K. lactis KU C RTQOKUKPI JQUV HQT RTQFWEVKQP QH TGEQODKPCPV RTQVGKP
þ5YKPMGNU GV CN. üùù3÷ )GNNKUUGP CPF *QNNGPDGTI üùù7÷ (NGGT, üùùûý, CPF þKXý VJG
HCEV VJCV K. lactis KU VJG UGEQPF [GCUV, DGUKFGU S. cerevisiae, HQT YJKEJ VJG )4#5
þgGPGTCNN[ rGICTFGF aU sCHGý UVCVWU JCU DGGP CRRTQXGF HQT HQQF CFFKVKXGU
þ$QPGMCOR CPF 1UVGTQO üùùò÷ %QGPGP GV CN. ûöööý.
K. lactis JCU DGGP CRRNKGF KP C PWODGT QH DKQVGEJPQNQIKECN RTQEGUUGU. -KNNGT
UVTCKPU JCXG DGGP WUGF KP OQFGN UKNCIG HGTOGPVCVKQPU CU CPVKÿ[GCUV CFFKVKXGU VQ
RTGXGPV URQKNCIG D[ NCEVKE CEKFÿWVKNK\KPI [GCUV EQPVCOKPCPVU þ-KVCOQVQ GV CN. üùùùý
QT KP ITCRG OWUV VQYCTFU KPFKIGPQWU [GCUV URGEKGU þ;CR GV CN. ûöööý. 2TQFWEVKQP QH
NCEVKE CEKF YCU CEJKGXGF D[ KPVTQFWEKPI C DQXKPG úÿNCEVCVG FGJ[FTQIGPCUG IGPG
CPF GPIKPGGTKPI R[TWXCVG OGVCDQNKUO þ2QTTQ GV CN. üùùùý.
6JG RTKOCT[ KPVGTGUV KP DKQVGEJPQNQIKECN CRRNKECVKQPU KU VQ WUG K. lactis CU C JQUV
HQT TGEQODKPCPV RTQVGKP RTQFWEVKQP, FGURKVG VJG HCEV VJCV KPXGUVOGPV QH VJG DKQVGEJ
KPFWUVT[ KPVQ CRRNKGF K. lactis TGUGCTEJ JCU FGENKPGF KP VJG RCUV DGECWUG QH VJG RCVÿ
GPV UKVWCVKQP. #P GCTN[ RCVGPV HKNGF KP üùõõ QP "Kluyveromyces CU C JQUV UVTCKP"
EQXGTGF CNN TGEQODKPCPV RTQVGKPU QDVCKPGF D[ IGPGVKE GPIKPGGTKPI KP VJKU QTICPKUO
þ©2 ö 3öü ø7ö $üý. 6JKU RCVGPV JCU CNNQYGF VQ FGXGNQR K. lactis KPVQ CP KPFWUVTKCN
UVTCKP HQT NCTIGÿUECNG EJ[OQUKP RTQFWEVKQP D[ )KUVÿ$TQECFGUñ&5/ÿ)KUV þ8CP FGP
$GTI GV CN. üùùö÷ 5YKPMGNU GV CN. üùù3ý. 6JTQWIJ ©ðÿHWPFKPI CPF PCVKQPCN ITCPVU,
TGEQODKPCPV RTQVGKP RTQFWEVKQP KP K. lactis JCU EQPVKPWGF VQ TGEGKXG EQPUKFGTCDNG
CVVGPVKQP KP CECFGOKEU YJGTG OQFGN RTQVGKPU þ5YGPPGP GV CN. ûööû÷ 5CNKQNC GV CN.
üùùù÷ 4QEJC GV CN. üùùø÷ )QP\CNG\ GV CN. üùù7ý CPF VQQNU YGTG FGXGNQRGF VJCV EQPÿ
HKTOGF VJG RQVGPVKCN QH PQPÿEQPXGPVKQPCN [GCUVU KP IGPGTCN CPF K. lactis KP RCTVKEWÿ
NCT. ðRQP FKTGEV EQORCTKUQP DGVYGGP S. cerevisiae CPF K. lactis CU JQUV U[UVGOU,
VJG NCVVGT RTQXGF UWRGTKQT KP C PWODGT QH ECUGU HQT TGCUQPU VJCV CTG PQV EQORNGVGN[
WPFGTUVQQF DWV RTQDCDN[ EQTTGNCVG YKVJ VJG DCNCPEG DGVYGGP QZKFCVKXG CPF HGTOGPÿ
VCVKXG OGVCDQNKUO. 6JG NCTIG TGRGTVQKTG QH RQUUKDKNKVKGU VQ KPVTQFWEG CPF GZRTGUU
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üù3

JGVGTQNQIQWU IGPGU KU CNUQ KORQTVCPV. 6JGUG KPENWFG OWNVKÿEQR[, UKPING EQR[, CPF
KPVGITCVKXG XGEVQTU, EQPUVKVWVKXG QT TGIWNCVGF RTQOQVGTU, CPF UGETGVKQP UKIPCNU þTGÿ
XKGYGF KP 9oUQNQYUMKÿúQWXGN GV CN. üùùø÷ )GNNKUUGP CPF *QNNGPDGTI üùù7÷ 5EJCHÿ
HTCVJ CPF $TGWPKI ûöööý. +P CFFKVKQP, VJG K. lactis RTQVGQN[VKE U[UVGO þ(NQTGU GV CN.
üùùùý CPF GP\[OGU VJCV KORTQXG RTQVGKP HQNFKPI þ$CQ CPF (WMWJCTC ûööüý JCXG
DGGP EJCTCEVGTK\GF. 4GUGCTEJ QP VJG IN[EQU[NCVKQP U[UVGO JCU TGXGCNGF HWTVJGT FKHÿ
HGTGPEGU VQ S. cerevisiae þúQRG\ÿ#XCNQU GV CN. ûööü÷ ðEEGNNGVVK GV CN. ûööö÷ ðEEGNÿ
NGVVK GV CN. ûööûý. 6JG Kluyveromyces lactis IGPQOG RTQLGEV RTQOKUGU VQ GPNCTIG
VJKU TGRGTVQKTG CPF VJWU GPJCPEG CRRNKECVKQP RQUUKDKNKVKGU.

üGHGTGPEGU

#UVTQO 5ð, -GIGN #, 5LQUVTCPF ì1, 4KPG ì þûöööý Kluyveromyces lactis 5KTûR TGIWNCVGU
ECVKQP UGPUKVKXKV[ CPF OCKPVCKPU C URGEKCNK\GF EJTQOCVKP UVTWEVWTG CV VJG ET[RVKE CNRJCÿ
NQEWU. )GPGVKEU:õüÿùü
#UVTQO 5ð, 4KPG ì þüùùõý 6JGOG CPF XCTKCVKQP COQPI UKNGPEKPI RTQVGKPU KP Saccharomyces
cerevisiae CPF Kluyveromyces lactis. )GPGVKEU üòõ:üöûüÿüöûù
$CLYC 9, 6QTEJKC 6©, *QRRGT ì© þüùõõý ;GCUV 4GIWNCVQT[ )GPG GAL3:%CTDQP 4GIWNCVKQP÷
ð#5)CN ©NGOGPVU KP %QOOQP YKVJ GAL1, GAL2, GAL7, GAL10, GAL80, CPF MEL1÷
©PEQFGF 2TQVGKP 5VTKMKPIN[ 5KOKNCT VQ ;GCUV CPF Escherichia coli )CNCEVQMKPCUGU. /QN
%GNN $KQN õ:3ò3ùÿ3òò7
$CQ 9), (WMWJCTC * þûööüý 5GETGVKQP QH JWOCP RTQVGKPU HTQO [GCUV:UVKOWNCVKQP D[ FWRNKÿ
ECVKQP QH RQN[WDKSWKVKP CPF RTQVGKP FKUWNHKFG KUQOGTCUG IGPGU KP Kluyveromyces lactis.
)GPG û7û:üö3ÿüüö
$CTKPCIC / þüùùòý ;GCUV GP\[OG HKPFU HCOG KP NKPM VQ &0# TGRNKECVKQP. 5EKGPEG ûøô:üü7ôÿ
üü7ø
$GVKPC 5, )QHHTKPK 2, (GTTGTQ +, 9oUQNQYUMKÿúQWXGN / þûööüý RAG4 IGPG GPEQFGU C INWÿ
EQUG UGPUQT KP Kluyveromyces lactis. )GPGVKEU üôõ:ôòüÿôòõ
$KCPEJK //, 5CPVCTGNNK 4, (TQPVCNK ú þüùùüý 2NCUOKF HWPEVKQPU KPXQNXGF KP VJG UVCDNG
RTQRCICVKQP QH VJG R-&ü EKTEWNCT RNCUOKF KP Kluyveromyces lactis. %WTT )GPGV üù:üôôÿ
üøü
$KCPEJK //, 6K\\CPK ú, &GUVTWGNNG /, (TQPVCNK ú, 9oUQNQYUMKÿúQWXGN / þüùùøý 6JG 'RGÿ
VKVGÿPGICVKXG' [GCUV Kluyveromyces lactis JCU C UKPING IGPG GZRTGUUKPI R[TWXCVG FGECTÿ
DQZ[NCUG CEVKXKV[. /QN /KETQDKQN üù:û7ÿ3ø
$KNNCTF 2, /oPCTV 5, $NCKUQPPGCW ì, $QNQVKPÿ(WMWJCTC /, (WMWJCTC *, 9oUQNQYUMKÿúQWXGN
/ þüùùøý )NWEQUG WRVCMG KP Kluyveromyces lactis:4QNG QH VJG HGT1 IGPG KP INWEQUG
VTCPURQTV. ì $CEVGTKQN ü7õ:ôõøöÿôõøø
$NCKUQPPGCW ì, (WMWJCTC *, 9oUQNQYUMKÿúQWXGN / þüùù7ý 6JG Kluyveromyces lactis
GSWKXCNGPV QH ECUGKP MKPCUG + KU TGSWKTGF HQT VJG VTCPUETKRVKQP QH VJG IGPG GPEQFKPI VJG
NQYÿCHHKPKV[ INWEQUG RGTOGCUG. /QN )GP )GPGV ûô3:òøùÿò77
$QNQVKPÿ(WMWJCTC /, 6QHHCPQÿ0KQEJG %, #TVKIWGPCXG (, &WEJCVGCWÿ0IW[GP ), úGOCKTG /,
/CTOGKUUG 4, /QPVTQEJGT 4, 4QDGTV %, 6GTOKGT /, 9KPEMGT 2, 9GUQNQYUMKÿúQWXGN /
þûöööý )GPQOKE GZRNQTCVKQP QH VJG JGOKCUEQO[EGVQWU [GCUVU:üü. Kluyveromyces lac-
tis. (©$5 úGVV òõ7:øøÿ7ö
$QPGMCOR (ì, 1UVGTQO ì þüùùòý 1P VJG UCHGV[ QH Kluyveromyces lactis:C TGXKGY. #RRN /Kÿ
ETQDKQN $KQVGEJPQN òü:üÿ3
üùò -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

$QWTICTGN &, 0IW[GP %%, $QNQVKPÿ(WMWJCTC / þüùùùý *#2ò, VJG INWEQUGÿTGRTGUUGF TGIWÿ
NCVGF UWDWPKV QH VJG *#2 VTCPUETKRVKQPCN EQORNGZ KPXQNXGF KP VJG HGTOGPVCVKQPÿ
TGURKTCVKQP UJKHV, JCU C HWPEVKQPCN JQOQNQIWG KP VJG TGURKTCVQT[ [GCUV Kluyveromyces
lactis. /QN /KETQDKQN 3ü:üûöôÿüûüô
$Q\\K #, 5CNKQNC /, (CNEQPG %, $QUUC (, /CTVKPK ( þüùù7ý 5VTWEVWTCN CPF DKQEJGOKECN UVWFÿ
KGU QH CNEQJQN FGJ[FTQIGPCUG KUQ\[OGU HTQO Kluyveromyces lactis. $KQEJKO $KQRJ[U
#EVC ü33ù:ü33ÿüòû
$TGOGT ì þüùõ3ý %CTPKVKPG:OGVCDQNKUO CPF HWPEVKQPU. 2J[UKQN 4GX ø3:üòûöÿüòõö
$TGWPKI -& þüùõùý )NWEQUG TGRTGUUKQP QH LAC IGPG GZRTGUUKQP KP [GCUV KU OGFKCVGF D[ VJG
VTCPUETKRVKQPCN CEVKXCVQT ú#%ù. /QN )GP )GPGV ûüø:òûûÿòû7
$TGWPKI -&, $QNQVKPÿ(WMWJCTC /, $KCPEJK //, $QWTICTGN &, (CNEQPG %, (GTTGTQ +, (TQPÿ
VCNK ú, )QHHTKPK 2, -TKLIGT ìì, /C\\QPK %, /KNMQYUMK %, 5VGGPUOC *;, 9GUQNQYUMKÿ
úQWXGN /, <GGOCP #/ þûöööý 4GIWNCVKQP QH RTKOCT[ ECTDQP OGVCDQNKUO KP Kluy-
veromyces lactis. ©P\[OG /KETQD 6GEJPQN ûø:77üÿ7õö
$TGWPKI -&, -WIGT 2 þüùõ7ý (WPEVKQPCN JQOQNQI[ DGVYGGP VJG [GCUV TGIWNCVQT[ RTQVGKPU
)#úò CPF ú#%ù:ú#%ùÿOGFKCVGF VTCPUETKRVKQPCN CEVKXCVKQP KP Kluyveromyces lactis
KPXQNXGU RTQVGKP DKPFKPI VQ C TGIWNCVQT[ UGSWGPEG JQOQNQIQWU VQ VJG )#úò RTQVGKPÿ
DKPFKPI UKVG. /QN %GNN $KQN 7:òòööÿòòöø
$TQPU ì(, &T[NC ##, 2NëIGT ©$©, 8KPMGPXNGWIGN 6/(, *QTPKI 0%&, )TKXGNN ú#, $NQO ì
þûööüý %CTDQP UQWTEGÿFGRGPFGPV VTCPUETKRVKQPCN TGIWNCVKQP QH VJG QCR8 IGPG KP Kluy-
veromyces lactis . %WTT )GPGV 3ù:3üüÿ3üõ
$WVNGT #4, 2QTVGT /, 5VCTM /ì4 þüùùüCý +PVTCEGNNWNCT GZRTGUUKQP QH Kluyveromyces lactis
VQZKP ICOOC UWDWPKV OKOKEU VTGCVOGPV YKVJ GZQIGPQWU VQZKP CPF FKUVKPIWKUJGU VYQ
ENCUUGU QH VQZKPÿTGUKUVCPV OWVCPV. ;GCUV 7:øü7ÿøûô
$WVNGT #4, 9JKVG ì*, 5VCTM /ì þüùùüDý #PCN[UKU QH VJG TGURQPUG QH Saccharomyces EGTGÿ
XKUKCG EGNNU VQ Kluyveromyces lactis VQZKP. ì )GP /KETQDKQN ü37 þ 2V 7ý:ü7òùÿü7ô7
%JCPI ;ÿ&, &KEMUQP 4% þüùõõý 2TKOCT[ UVTWEVWTG QH VJG NCEVQUG RGTOGCUG IGPG HTQO VJG
[GCUV Kluyveromyces lactis. ì $KQN %JGO ûø3:üøøùøÿüø7ö3
%JGP îì þüùù7ý %NQPKPI CPF EJCTCEVGTK\CVKQP QH VJG NKRQ[NÿRTQVGKP NKICUG IGPG LIPB HTQO
VJG [GCUV Kluyveromyces lactis:5[PGTIKUVKE TGURKTCVQT[ FGHKEKGPE[ FWG VQ OWVCVKQPU KP
LIPB CPF OKVQEJQPFTKCN (üÿ#62CUG UWDWPKVU. /QN )GP )GPGV ûôô:3òüÿ3òù
%JGP îì, $KCPEJK //, 5WFC -, (WMWJCTC * þüùõùý 6JG JQUV TCPIG QH VJG R-&üÿFGTKXGF
RNCUOKFU KP [GCUV. %WTT )GPGV üø:ùôÿùõ
%JGP îì, %NCTMÿ9CNMGT )& þüùù3ý /WVCVKQPU KP MGI IGPGU EQPXGTV Kluyveromyces lactis
KPVQ C RGVKVGÿRQUKVKXG [GCUV. )GPGVKEU ü33:ôü7ÿôûô
%JGP îì, *CPUDTQ 2/, %NCTMÿ9CNMGT )& þüùùõý 5WRRTGUUKQP QH þTJQýö NGVJCNKV[ D[ OKVQÿ
EJQPFTKCN #62U[PVJCUG (ü OWVCVKQPU KP Kluyveromyces lactis QEEWTU KP VJG CDUGPEG QH
(ö. /QN )GP )GPGV ûôù:òô7ÿòø7
%JGP îì, 5CNKQNC /, (CNEQPG %, $KCPEJK //, (WMWJCTC * þüùõøý 5GSWGPEG 1TICPK\CVKQP
QH VJG %KTEWNCT 2NCUOKF R-&ü HTQO VJG ;GCUV Kluyveromyces drosophilarum. 0WENGKE
#EKFU 4GU üò:òò7üÿòòõü
%JGP îì, 9oUQNQYUMKÿúQWXGN /, (WMWJCTC * þüùùûý )NWEQUG VTCPURQTV KP VJG [GCUV Kluy-
veromyces lactis. ++ 6TCPUETKRVKQPCN TGIWNCVKQP QH VJG INWEQUG VTCPURQTVGT IGPG RAG1.
/QN )GP )GPGV û33:ù7ÿüöô
%NCTMG ú þüùùõý %GPVTQOGTGU:RTQVGKPU, RTQVGKP EQORNGZGU, CPF TGRGCVGF FQOCKPU CV EGPÿ
VTQOGTGU QH UKORNG GWMCT[QVGU. %WTT 1RKP )GPGV &GX õ:ûüûÿûüõ
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üùô

%QGPGP 6/, $GTVGPU #/, FG *QQI 5%, 8GTURGGMÿ4KR %/ þûöööý 5CHGV[ GXCNWCVKQP QH C
NCEVCUG GP\[OG RTGRCTCVKQP FGTKXGF HTQO Kluyveromyces lactis. (QQF %JGO 6QZKEQN
3õ:ø7üÿø77
%QORCIPQ %, $QUEJK (, &CNGHHG #, 2QTTQ &, 4CP\K $/ þüùùùý +UQNCVKQP, PWENGQVKFG UGÿ
SWGPEG, CPF RJ[UKQNQIKECN TGNGXCPEG QH VJG IGPG GPEQFKPI VTKQUG RJQURJCVG KUQOGTCUG
HTQO Kluyveromyces lactis. #RRN ©PXKTQPO /KETQDKQN øô:òûüøÿòûüù
%\[\ /, 0CIKGE //, &KEMUQP 4% þüùù3ý #WVQTGIWNCVKQP QH GAL4 VTCPUETKRVKQP KU GUUGPVKCN
HQT TCRKF ITQYVJ QH Kluyveromyces lactis QP NCEVQUG CPF ICNCEVQUG. 0WENGKE #EKFU 4GU
ûü:ò37õÿò3õû
&GUVTWGNNG /, /GPIJKPK 4, (TQPVCNK ú, $KCPEJK // þüùùùý 4GIWNCVKQP QH VJG GZRTGUUKQP QH
VJG Kluyveromyces lactis PDC1 IGPG:ECTDQP UQWTEGÿTGURQPUKXG GNGOGPVU CPF CWVQTGIWÿ
NCVKQP. ;GCUV üô:3øüÿ37ö
&KEMUQP 4%, $CTT - þüùõ3ý %JCTCEVGTK\CVKQP QH úCEVQUG 6TCPURQTV KP Kluyveromyces lactis.
ì $CEVGTKQN üôò:üûòôÿüûôü
&QPI ì, &KEMUQP 4% þüùù7ý )NWEQUG TGRTGUUGU VJG NCEVQUGÿICNCEVQUG TGIWNQP KP Kluyvero-
myces lactis VJTQWIJ C SNF1 CPF MIG1-FGRGPFGPV RCVJYC[ VJCV OQFWNCVGU ICNCEVQÿ
MKPCUG þGAL1ý IGPG GZRTGUUKQP. 0WEN #EKFU 4GU ûô:3øô7ÿ3øøò
&QTUOCP ì%, 8CP *GGUYKLM 9%, )TKXGNN ú# þüùùöý ;GCUV IGPGTCN VTCPUETKRVKQP HCEVQT
)(ü:UGSWGPEG TGSWKTGOGPVU HQT DKPFKPI VQ &0# CPF GXQNWVKQPCT[ EQPUGTXCVKQP. 0WEN
#EKFU 4GU üõ:û7øùÿû77ø
©PVKCP -&, $CTPGVV ì# þüùõ3ý 5QOG IGPGVKECN CPF DKQEJGOKECN CVVGORVU VQ GNWEKFCVG VJG
GPGTIGVKEU QH UWICT WRVCMG CPF GZRNCKP VJG -NW[XGT GHHGEV KP VJG [GCUV Kluyveromyces
lactis. %WTT )GPGV 7:3û3ÿ3ûô
(GNNQYU ì, ©TFLWOGPVÿ$TQOCIG *, 6GORUV 2, 5XGLUVTWR ìí þûöööý 6JG ©NRû UWDWPKV QH
GNQPICVQT CPF GNQPICVKPI 40# RQN[OGTCUG ++ JQNQGP\[OG KU C 9&òö TGRGCV RTQVGKP. ì
$KQN %JGO û7ô:üûõùøÿüûõùù
(GTTGTQ +, 8KQNC #/, )QHHGCW # þüùõüý +PFWEVKQP D[ INWEQUG QH CP CPVKO[EKPÿKPUGPUKVKXG,
C\KFGÿUGPUKVKXG TGURKTCVKQP KP VJG [GCUV Kluyveromyces lactis. #PVQPKG XCP úGGWYGPÿ
JQGM ò7:üüÿûò
(KEJVPGT ú, (TQJNQHH (, $WTMPGT -, úCTUGP /, $TGWPKI -&, 5EJCHHTCVJ 4 þûööûý /QNGEWNCT
CPCN[UKU QH KTI12/TOT4, C Saccharomyces cerevisiae IGPG TGSWKTGF HQT Kluyveromyces
lactis \[OQEKP CEVKQP. /QN /KETQDKQN ò3:7õ3ÿ7ùü
(NGGT 4 þüùùûý ©PIKPGGTKPI [GCUV HQT JKIJ NGXGN GZRTGUUKQP. %WTT 1RKP $KQVGEJPQN 3:òõøÿ
òùø
(NKMYGGTV /6, <CPFGP úXF, ìCPUUGP 9/6, 5VGGPUOC *;, 8CP &KLMGP ì2, 2TQPM ì6 þüùùøý
2[TWXCVG FGECTDQZ[NCUG:CP KPFKURGPUKDNG GP\[OG HQT ITQYVJ QH Saccharomyces cere-
visiae QP INWEQUG. ;GCUV üû:ûò7ÿûô7
(NQTGU /8, %WGNNCU #, 8QIGV %© þüùùùý 6JG RTQVGQN[VKE U[UVGO QH VJG [GCUV Kluyveromyces
lactis. ;GCUV üô:üò37ÿüòòõ
(NQTGU %ÿú, 4QFTsSWG\ %, 2GVKV 6, )CPEGFQ % þûöööý %CTDQJ[FTCVG CPF GPGTI[ÿ[KGNFKPI OGÿ
VCDQNKUO KP PQPÿEQPXGPVKQPCN [GCUVU. (©/5 /KETQDKQN 4GX ûò:ôö7ÿôûù
(QWTPKGT #, (NGGT 4, ;GJ 2, /C[CWZ ì( þüùùöý 6JG RTKOCT[ UVTWEVWTG QH VJG 3ÿ
RJQURJQIN[EGTCVG MKPCUG þ2)-ý IGPG HTQO Kluyveromyces lactis. 0WEN #EKFU 4GU
üõ:3øôÿ3øô
(TGKTGÿ2KEQU /#, *QNNGPDGTI %2, $TGWPKI -&, %GTFhP /© þüùùôý 4GIWNCVKQP QH E[VQÿ
EJTQOG c GZRTGUUKQP KP VJG CGTQDKE TGURKTCVQT[ [GCUV Kluyveromyces lactis. (©$5 úGVV
3øö:3ùÿòû
üùø -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

(TGKTGÿ2KEQU /#, 4QFTKSWG\ÿ6QTTGU #/, 4COKN ©, %GTFCP /©, $TGWPKI -&, *QNNGPDGTI
%2, <KVQOGT 45 þüùù3ý 5GSWGPEG QH C E[VQEJTQOG c IGPG HTQO Kluyveromyces lactis
CPF KVU WRUVTGCO TGIKQP. ;GCUV ù:ûöò
(TQJNQHH (, ìCDNQPQYUMK &, (KEJVPGT ú, 5EJCHHTCVJ 4 þûöö3ý 5WDWPKV %QOOWPKECVKQPU %TWÿ
EKCN HQT VJG (WPEVKQPCN +PVGITKV[ QH VJG ;GCUV 40# 2QN[OGTCUG ++ ©NQPICVQT þICOOC ÿ
6QZKP 6CTIGV þ616ýý %QORNGZ. ì $KQN %JGO û7õ:ùôøÿùøü
)DGNUMC ;, *QTXhVJQXh -, #CTV íì/XF, <QPPGXGNF $ì/, 5VGGPUOC *;, 5WDsM ì þüùùøý
+UQNCVKQP CPF OQNGEWNCT CPCN[UKU QH VJG IGPG HQT E[VQEJTQOG c1 HTQO Kluyveromyces
lactis. %WTT )GPGV 3ö:üòôÿüôö
)DGNUMC ;, 1DGTPCWGTQXC /, 5WDsM ì þüùùùý )TQYVJ QH GWMCT[QVKE EGNNU KP TGNCVKQP VQ VJG
UVTWEVWTG QH OKVQEJQPFTKCN OGODTCPGU CPF OKVQEJQPFTKCN IGPQOG. (QNKC /KETQDKQN
òò:øù7ÿ7öû
)GNNKUUGP ), *QNNGPDGTI %2 þüùù7ý #RRNKECVKQP QH [GCUVU KP IGPG GZRTGUUKQP UVWFKGU:C EQOÿ
RCTKUQP QH Saccharomyces cerevisiae, Hansenula polymorpha CPF Kluyveromyces lac-
tis ÿÿ C TGXKGY. )GPG üùö:õ7ÿù7
)GQTKU +, %CUUCTV ìÿ2, $TGWPKI -&, 8CPFGPJCWVG ì þüùùùý )NWEQUG TGRTGUUKQP QH VJG Kluy-
veromyces lactis KPXGTVCUG IGPG KlINV1FQGU PQV TGSWKTG /KIüR. /QN )GP )GPGV
ûøü:õøûÿõ7ö
)GQTKU +, -TKLIGT ìì, $TGWPKI -&, 8CPFGPJCWVG ì þûöööý &KHHGTGPEGU KP TGIWNCVKQP QH [GCUV
INWEQPGQIGPGUKU TGXGCNGF D[ %CVõRÿKPFGRGPFGPV CEVKXCVKQPQH PCK1 CPF FBP1 IGPGU KP
Kluyveromyces lactis. /QN )GP )GPGV ûøò:üù3ÿûö3
)JCN[ #©, $GPÿ*CUUCP 4/, /CPUQWT /*, 0CUUCT /# þüùù3ý /QFGNKPI DCVEJ RTQFWEVKQP
QH UKPING EGNN RTQVGKP HTQO EJGGUG YJG[, ++:úCEVQUG OGVCDQNKUO. #RRN $KQEJGO $KQÿ
VGEJPQN ò3:üôÿûò
){FGEMG #, <CEJCTKCG 9, #TXCPKVKFKU #, $TGWPKI -& þüùùüý %QTGIWNCVKQP QH VJG Kluy-
veromyces lactis NCEVQUG RGTOGCUG CPF ¾ÿICNCEVQUKFCUG IGPGU KU CEJKGXGF D[ KPVGTCEVKQP
QH OWNVKRNG ú#%ù DKPFKPI UKVGU KP C û.ø MDR FKXGTIGPV RTQOQVGT. 0WENGKE #EKFU 4GU
üù:ô3ôüÿô3ôõ
)QHHTKPK 2, #NIGTK ##, &QPPKPK %, 9oUQNQYUMKÿúQWXGN /, (GTTGTQ + þüùõùý RAG1 CPF
RAG2:PWENGCT IGPGU KPXQNXGF KP VJG FGRGPFGPEGñKPFGRGPFGPEG QP OKVQEJQPFTKCN TGURKÿ
TCVQT[ HWPEVKQP HQT ITQYVJ QP UWICTU. ;GCUV ô:ùùÿüöø
)QHHTKPK 2, (KECTGNNK #, &QPPKPK %, úQFK 6, 2WINKUK 22, (GTTGTQ + þüùùøý FOG1 CPF FOG2
IGPGU, TGSWKTGF HQT VJG VTCPUETKRVKQPCN CEVKXCVKQP QH INWEQUGÿTGRTGUUKDNG IGPGU QH Kluy-
veromyces lactis, CTG JQOQNQIQWU VQ GAL83 CPF SNF1 QH Saccharomyces cerevisiae.
%WTT )GPGV ûù:3üøÿ3ûø
)QHHTKPK 2, (KECTGNNK #, (GTTGTQ + þüùùôý *GZQMKPCUG CEVKXKV[ KU CHHGEVGF KP OWVCPVU QH Kluy-
veromyces lactis TGUKUVCPV VQ INWEQUG TGRTGUUKQP. /KETQDKQNQI[ üòü:òòüÿòò7
)QHHTKPK 2, 9oUQNQYUMKÿúQWXGN /, (GTTGTQ + þüùùüý # RJQURJQINWEQUG KUQOGTCUG IGPG KU
KPXQXGF KP VJG 4CI RJGPQV[RG QH VJG [GCUV Kluyveromyces lactis. /QN )GP )GPGV
ûûõ:òöüÿòöù
)QHHTKPK 2, 9oUQNQYUMKÿúQWXGN /, (GTTGTQ +, (WMWJCTC * þüùùöý RAG1 IGPG QH VJG [GCUV
Kluyveromyces lactis EQFGU HQT C UWICT VTCPURQTVGT. 0WEN #EKFU 4GU üõ:ôûùòÿôûùò
)QPECNXGU 2/, /CWTGT -, /CIGT 9*, 2NCPVC 4ì þüùùûý Kluyveromyces EQPVCKPU C HWPEÿ
VKQPCN #$(üÿJQOQNQIWG. 0WEN #EKFU 4GU ûö:ûûüüÿûûüô
)QP\CNG\ (ì, /QPVGU ì, /CTVKP (, úQRG\ /%, (GTOKPCP ©, %CVCNCP ì, )CNCP /#,
&QOKPIWG\ # þüùù7ý /QNGEWNCT ENQPKPI QH 6X&#1ü, C IGPG GPEQFKPI C &ÿCOKPQ CEKF
QZKFCUG HTQO Trigonopsis variabilis CPF KVU GZRTGUUKQP KP Saccharomyces cerevisiae
CPF Kluyveromyces lactis. ;GCUV ü3:ü3ùùÿõ
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üù7

)QP\hNG\ÿ&QOKPIWG\ /, (TGKTGÿ2KEQU /#, 4COKN ©, )WKCTF $, %GTFhP /© þûöööý *GOGÿ

OGFKCVGF VTCPUETKRVKQPCN EQPVTQN KP Kluyveromyces lactis. %WTT )GPGV 3õ:ü7üÿü77
)QP\hNG\ÿ&QOKPIWG\ /, /oPFG\ %CTTQ %, %GTFhP /© þüùù7ý +UQNCVKQP CPF EJCTCEVGTK\Cÿ
VKQP QH VJG KlHEM1 IGPG KP Kluyveromyces lactis.;GCUV ü3:ùøüÿù7ü
)QP\hNG\ 5KUQ /+, (TGKTG 2KEQU /#, %GTFhP /© þüùùøý 4GQZKFCVKQP QH VJG 0#&2* RTQÿ
FWEGF D[ VJG RGPVQUG RJQURJCVG RCVJYC[ KU PGEGUUCT[ HQT VJG WVKNK\CVKQP QH INWEQUG D[
Kluyveromyces lactis rag2 OWVCPVU. (©$5 úGVV 3õ7:7ÿüö
)QP\hNG\ 5KUQ /+, 4COKN ©, %GTFhP /©, (TGKTGÿ2KEQU /# þüùùøý 4GURKTQHGTOGPVCVKXG OGÿ
VCDQNKUO KP Kluyveromyces lactis:©VJCPQN RTQFWEVKQP CPF VJG %TCDVTGG GHHGEV. ©P\[OG
/KETQDKCN 6GEJPQN üõ:ôõôÿôùü
)TCJCO +4, *CY 4#, 5RKPM -), *CNFGP -#, %JCODGTU # þüùùùý +P XKXQ CPCN[UKU QH HWPEÿ
VKQPCN TGIKQPU YKVJKP [GCUV 4CRüR. /QN %GNN $KQN üù:7òõüÿ7òùö
)WKNNGP ©, #DGKLQP %, *KTUEJDGTI %$ þüùùùý 6JG IGPGU HQT VJG )QNIK CRRCTCVWU 0ÿ
CEGV[NINWEQUCOKP[NVTCPUHGTCUG CPF VJG ð&2ÿ0ÿCEGV[NINWEQUCOKPG VTCPURQTVGT CTG EQPÿ
VKIWQWU KP Kluyveromyces lactis. ì $KQN %JGO û7ò:øøòüÿøøòø
)WPIG 0 þüùõøý úKPGCT &0# MKNNGT RNCUOKFU HTQO VJG [GCUV Kluyveromyces. ;GCUV û:üô3ÿ
üøû
)WPIG 0, 5CMCIWEJK - þüùõüý +PVGTIGPGTKE VTCPUHGT QH FGQZ[TKDQPWENGKE CEKF MKNNGT RNCUÿ
OKFU, R)-Nü CPF R)-Nû, HTQO Kluyveromyces lactis KPVQ Saccharomyces cerevisiae D[
EGNN HWUKQP. ì $CEVGTKQN üò7:üôôÿüøö
)WPIG 0, 6COCTW #, 1\CYC (, 5CMCIWEJK - þüùõüý +UQNCVKQP CPF EJCTCEVGTK\CVKQP QH NKPGCT
FGQZ[TKDQPWENGKE CEKF RNCUOKFU HTQO Kluyveromyces lactis CPF VJG RNCUOKFÿCUUQEKCVGF
MKNNGT EJCTCEVGT. ì $CEVGTKQN üòô:3õûÿ3ùö
*CY 4, ;CTTCIWFK #&, ðGOWTC * þûööüý +UQNCVKQP QH GCR1, C OCLQT VTCPUETKRVKQP HCEVQT QH
IN[EQN[VKE IGPGU KP Saccharomyces cerevisiae, HTQO Kluyveromyces lactis. ;GCUV
üõ:7ûùÿ73ô
*GKPKUEJ ì, -KTEJTCVJ ú, úKGUGP 6, 8QIGNUCPI -, *QNNGPDGTI %2 þüùù3ý /QNGEWNCT IGPGVKEU
QH RJQURJQHTWEVQMKPCUG KP VJG [GCUV Kluyveromyces lactis. /QN /KETQDKQN õ:ôôùÿô7ö
*GTOCP #, 4QOCP * þüùøøý #NNGNG URGEKHKE FGVGTOKPCPVU QH JQOQVJCNNKUO KP Saccharomy-
ces lactis. )GPGVKEU ô3:7û7ÿ7òö
*GWU ìì, <QPPGXGNF $ì, 5VGGPUOC *;, 8CP FGP $GTI ì# þüùùòý /WVCVKQPCN CPCN[UKU QH EGPÿ
VTQOGTKE &0# GNGOGPVU QH Kluyveromyces lactis CPF VJGKT TQNG KP FGVGTOKPKPI VJG URGÿ
EKGU URGEKHKEKV[ QH VJG JKIJN[ JQOQNQIQWU EGPVTQOGTGU HTQO K. lactis CPF Saccharomy-
ces cerevisiae. /QN )GP )GPGV ûò3:3ûôÿ333
+DQTTC (, $CNN // þüùùòý Kluyveromyces marxianus UOCNN &0# HTCIOGPVU EQPVCKP DQVJ
CWVQPQOQWU TGRNKECVKXG CPF EGPVTQOGTKE GNGOGPVU VJCV CNUQ HWPEVKQP KP Kluyveromyces
lactis. ;GCUV üö:üøûüÿüøûù
ìCDNQPQYUMK &, (KEJVPGT ú, /CTVKP 8ì, -NCUUGP 4, /GKPJCTFV (, 5VCTM /ì, 5EJCHHTCVJ 4
þûööüý Saccharomyces cerevisiae EGNN YCNN EJKVKP, VJG Kluyveromyces lactis \[OQEKP
TGEGRVQT. ;GCUV üõ:üûõôÿüûùù
ìCEQD[ ì, *QNNGPDGTI %2, *GKPKUEJ ìì þüùù3ý 6TCPUCNFQNCUG OWVCPVU KP VJG [GCUV Kluyvero-
myces lactis RTQXKFG GXKFGPEG VJCV INWEQUG ECP DG OGVCDQNK\GF VJTQWIJ VJG RGPVQUG
RJQURJCVG RCVJYC[. /QN /KETQDKQN üö:õø7ÿõ7ø
ìCEQD[ ìì, *GKPKUEJ ìì þüùù7ý #PCN[UKU QH C VTCPUMGVQNCUG IGPG HTQO Kluyveromyces lactis
TGXGCNU VJCV VJG [GCUV GP\[OGU CTG OQTG TGNCVGF VQ VTCPUMGVQNCUG QH RTQMCT[QVKE QTKIKPU
VJCP VJQUG QH JKIJGT GWMCT[QVGU. %WTT )GPGV 3ü:üôÿûü
-GQIJ 45, 5GQKIJG %, 9QNHG -* þüùùõý ©XQNWVKQP QH IGPG QTFGT CPF EJTQOQUQOG PWODGT
KP Saccharomyces, Kluyveromyces CPF TGNCVGF HWPIK. ;GCUV üò:òò3ÿòô7
üùõ -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

-KGTU ì, <GGOCP #/, úWVVKM /, 6JKGNG %, %CUVTKNNQ ì+, 5VGGPUOC *;, 8CP &KLMGP ì2, 2TQPM
ì6 þüùùõý 4GIWNCVKQP QH CNEQJQNKE HGTOGPVCVKQP KP DCVEJ CPF EJGOQUVCV EWNVWTGU QH
Kluyveromyces lactis %$5 û3ôù. ;GCUV üò:òôùÿòøù
-KVCFC -, )WPIG 0 þüùõõý 2CNKPFTQOGÿJCKTRKP NKPGCT RNCUOKFU RQUUGUUKPI QPN[ C RCTV QH VJG
14(ü IGPG QH VJG [GCUV MKNNGT RNCUOKF R)-úü. /QN )GP )GPGV ûüô:òøÿôû
-KVCICYC -, *KGVGT 2 þûööüý ©XQNWVKQPCT[ EQPUGTXCVKQP DGVYGGP DWFFKPI [GCUV CPF JWOCP
MKPGVQEJQTGU. 0CV 4GX /QN %GNN $KQN û:ø7õÿøõ7
-KVCOQVQ *-, *CUGDG #, 1JOQOQ 5, 5WVQ ©), /WTCMK /, +KOWTC ; þüùùùý 2TGXGPVKQP QH
CGTQDKE URQKNCIG QH OCK\G UKNCIG D[ C IGPGVKECNN[ OQFKHKGF MKNNGT [GCUV, Kluyveromyces
lactis, FGHGEVKXG KP VJG CDKNKV[ VQ ITQY QP NCEVKE CEKF. #RRN ©PXKTQP /KETQDKQN øô:òøù7ÿ
ò7öö
-KVCOQVQ *-, 1JOQOQ 5, +KOWTC ; þüùùõý +UQNCVKQP CPF PWENGQVKFG UGSWGPEG QH VJG IGPG
GPEQFKPI RJQURJQGPQNR[TWXCVG ECTDQZ[MKPCUG HTQO Kluyveromyces lactis. ;GCUV
üò:ùø3ÿùø7
-QJNJCY )$, 6CPÿ9KNUQP # þüù77ý %CTPKVKPG CEGV[NVTCPUHGTCUG:ECPFKFCVG HQT VJG VTCPUHGT QH
CEGV[N ITQWRU VJTQWIJ VJG OKVQEJQPFTKCN OGODTCPG. ì $CEVGTKQN üûù:üüôùÿüüøü
-WTV\OCP %2, 4QDPGVV %ì þüùùõý +FGPVKHKECVKQP CPF RJ[NQIGP[ QH CUEQO[EGVQWU [GCUVU
HTQO CPCN[UKUK QH PWENGCT NCTIG UWDWPKV þûø5ý TKDQUQOCN &0# RCTVKCN UGSWGPEGU. #Pÿ
VQPKG 8CP úGGWYGPJQGM 73:33üÿ37ü
úCTUGP /, )WPIG 0, /GKPJCTFV ( þüùùõý Kluyveromyces lactis MKNNGT RNCUOKF R)-úû:GXKÿ
FGPEG HQT C XKTCNÿNKMG ECRRKPI GP\[OG GPEQFGF D[ 14(3. 2NCUOKF òö:ûò3ÿûòø

úCTUQP )2, %CUVCPQVVQ &, 4QUUK ìì, /CNCHC 2 þüùùòý +UQNCVKQP CPF HWPEVKQPCN CPCN[UKU QH C
Kluyveromyces lactis 4#2ü JQOQNQIWG. )GPG üôö:3ôÿòü
úGOCKTG /, )W[QP #, $GVKPC 5, 9oUQNQYUMKÿúQWXGN / þûööûý 4GIWNCVKQP QH IN[EQN[UKU D[
ECUGKP MKPCUG + þ4CIõRý KP Kluyveromyces lactis KPXQNXGU C &0#ÿDKPFKPI RTQVGKP,
5EMüR, C JQOQNQIWG QH 5IEüR QH Saccharomyces cerevisiae. %WTT )GPGV òö:3ôôÿ3øò
úGQPCTFQ ì/, $JCKTK 5/, &KEMUQP 4% þüùõ7ý +FGPVKHKECVKQP QH ðRUVTGCO #EVKXCVQT 5Gÿ
SWGPEGU 6JCV 4GIWNCVG +PFWEVKQP QH VJG ¾ÿ)CNCEVQUKFCUG )GPG KP Kluyveromyces lactis.
/QN %GNN $KQN 7:ò3øùÿò37ø
úNQTGPVG $, &WTTGPU 2, /CNRGTVW[ #, #KING /, #TVKIWGPCXG (, $NCPFKP ), $QNQVKPÿ(WMWJCTC
/, $QP ©, $TQVVKGT 2, %CUCTGIQNC 5, &WLQP $, FG /QPVKIP[ ì, úGRKPING #, 0GWXGINKUG
%, 1\KGTÿ-CNQIGTQRQWNQU 1, 2QVKGT 5, 5CWTKP 9, 6GMCKC (, 6QHHCPQÿ0KQEJG %, 9GUQÿ
NQYUMKÿúQWXGN /, 9KPEMGT 2, 9GKUUGPDCEJ ì, 5QWEKGV ì, )CKNNCTFKP % þûöööCý )Gÿ
PQOKE GZRNQTCVKQP QH VJG JGOKCUEQO[EGVQWU [GCUVU:ûö. ©XQNWVKQP QH IGPG TGFWPFCPE[
EQORCTGF VQ Saccharomyces cerevisiae. (©$5 úGVV òõ7:üûûÿü33
úNQTGPVG $, /CNRGTVW[ #, 0GWXGINKUG %, FG /QPVKIP[ ì, #KING /, #TVKIWGPCXG (, $NCPFKP
), $QNQVKPÿ(WMWJCTC /, $QP ©, $TQVVKGT 2, %CUCTGIQNC 5, &WTTGPU 2, )CKNNCTFKP %,
úGRKPING #, 1\KGTÿ-CNQIGTQRQWNQU 1, 2QVKGT 5, 5CWTKP 9, 6GMCKC (, 6QHHCPQÿ0KQEJG
%, 9GUQNQYUMKÿúQWXGN /, 9KPEMGT 2, 9GKUUGPDCEJ ì, 5QWEKGV ì, &WLQP $ þûöööDý
)GPQOKE GZRNQTCVKQP QH VJG JGOKCUEQO[EGVQWU [GCUVU:üõ. %QORCTCVKXG CPCN[UKU QH
EJTQOQUQOG OCRU CPF U[PVGP[ YKVJ Saccharomyces cerevisiae. (©$5 úGVV òõ7:üöüÿ
üüû
úQFK 6, )QHHTKPK 2, $QNQPFK +, (GTTGTQ + þüùùõý 6TCPUETKRVKQPCN TGIWNCVKQP QH VJG KlDLD
IGPG, GPEQFKPI VJG OKVQEJQPFTKCN GP\[OG &ÿNCEVCVG HGTTKE[VQEJTQOG E QZKFQTGFWEVCUG
KP Kluyveromyces lactis:GHHGEV QH Klhap2 CPF fog OWVCVKQPU. %WTT )GPGV 3ò:üûÿûö
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP üùù

úQFK 6, 5CNKQNC /, &QPPKPK %, )QHHTKPK 2 þûööüý 6JTGG VCTIGV IGPGU HQT VJG VTCPUETKRVKQPCN
CEVKXCVQT %CVõR QH Kluyveromyces lactis:#EGV[N EQGP\[OG # U[PVJGVCUG IGPGU KLACS1
CPF KlACS2 CPF NCEVCVG RGTOGCUG IGPG KlJEN1. ì $CEVGTKQN üõ3:ôûô7ÿôûøü
úQRG\ÿ#XCNQU /&, ðEEGNNGVVK &, #DGKLQP %, *KTUEJDGTI %$ þûööüý 6JG ð&2CUG CEVKXKV[ QH
VJG Kluyveromyces lactis )QNIK )&2CUG JCU C TQNG KP WTKFKPG PWENGQVKFG UWICT VTCPURQTV
KPVQ )QNIK XGUKENGU. )N[EQDKQNQI[ üü:òü3ÿòûû
úW[VGP -, FG -QPKPI 9, 6GUUGWT +, 4WK\ /%, 4COQU ì, %QDDCGTV 2, 6JGXGNGKP ì/, *QJÿ
OCPP 5 þüùù3ý &KUTWRVKQP QH VJG Kluyveromyces lactis GGS1 IGPG ECWUGU KPCDKNKV[ VQ
ITQY QP INWEQUG CPF HTWEVQUG CPF KU UWRRTGUUGF D[ OWVCVKQPU VJCV TGFWEG UWICT WRVCMG.
©WT ì $KQEJGO ûü7:7öüÿ7ü3
/CWNNW %, úCORKU ), $CUKNG 6, +PIKCPPK #, 4QUUQNKPK )/, 2QORGK 4 þüùùùý 2TQFWEVKQP QH
N[UQ\[OGÿGPTKEJGF DKQOCUU HTQO EJGGUG KPFWUVT[ D[ÿRTQFWEVU. ì #RRN /KETQDKQN
õø:üõûÿüõø
/E©CEJGTP /ì, -TCWUMQRH #, $NCEMDWTP ©* þûöööý 6GNQOGTGU CPF VJGKT EQPVTQN. #PPW
4GX )GPGV 3ò:33üÿ3ôõ
/E©CEJGTP /ì, ðPFGTYQQF &*, $NCEMDWTP ©* þûööûý &[PCOKEU QH VGNQOGTKE &0# VWTPÿ
QXGT KP [GCUV. )GPGVKEU üøö:ø3ÿ73
/E0GGN &), 6COCPQK ( þüùùüý 6GTOKPCN TGIKQP TGEQIPKVKQP HCEVQT ü, C &0#ÿDKPFKPI RTQÿ
VGKP TGEQIPK\KPI VJG KPXGTVGF VGTOKPCN TGRGCVU QH VJG R)-N NKPGCT &0# RNCUOKFU. 2TQE
0CVN #ECF 5EK ð 5 # õõ:üü3ùõÿüüòöû
/GKPJCTFV (, 5EJCHHTCVJ 4, úCTUGP / þüùù7ý /KETQDKCN NKPGCT RNCUOKFU. #RRN /KETQDKQN
$KQVGEJPQN ò7:3ûùÿ33ø
/GNNQT ì, ìKCPI 9, (WPM /, 4CVJLGP ì, $CTPGU %#, *KP\ 6, *GIGOCPP ì*, 2JKNKRRUGP 2
þüùùöý %2(ü, C [GCUV RTQVGKP YJKEJ HWPEVKQPU KP EGPVTQOGTGU CPF RTQOQVGTU. ©/$1 ì
ù:òöü7ÿòöûø
/G[GT ì, 9CNMGTÿìQPCJ #, *QNNGPDGTI %2 þüùùüý )CNCEVQMKPCUG GPEQFGF D[ GAL1 KU C DKÿ
HWPEVKQPCN RTQVGKP TGSWKTGF HQT KPFWEVKQP QH VJG GAL IGPGU KP Kluyveromyces lactis CPF
KU CDNG VQ UWRRTGUU VJG gal3 RJGPQV[RG KP Saccharomyces cerevisiae. /QN %GNN $KQN
üü:ôòôòÿôòøü
/KNMQYUMK %, -TCORG 5, 9GKTKEJ ì, *CUUG 8, $QNGU ©, $TGWPKI -& þûööüý (GGFDCEM TGIWÿ
NCVKQP QH INWEQUG VTCPURQTVGT IGPG VTCPUETKRVKQP KP Kluyveromyces lactis D[ INWEQUG WRÿ
VCMG. ì $CEVGTKQN üõ3:ôûû3ÿôûûù
/WNFGT 9, 5EJQNVGP +*ì/, FG $QGT 49, )TKXGNN ú# þüùùòý 5GSWGPEG QH VJG *#23 VTCPÿ
UETKRVKQP HCEVQT QH Kluyveromyces lactis RTGFKEVU VJG RTGUGPEG QH C PQXGN òÿE[UVGKPG
\KPEÿHKPIGT OQVKH. /QN )GP )GPGV ûòô:ùøÿüöø
/WNFGT 9, 5EJQNVGP +*ì/, )TKXGNN ú# þüùùôCý %CTDQP ECVCDQNKVG TGIWNCVKQP QH VTCPUETKRÿ
VKQP QH PWENGCT IGPGU EQFKPI HQT OKVQEJQPFTKCN RTQVGKPU KP Kluyveromyces lactis. %WTT
)GPGV ûõ:ûø7ÿû73
/WNFGT 9, 5EJQNVGP +*, )TKXGNN ú# þüùùôDý &KUVKPEV VTCPUETKRVKQPCN TGIWNCVKQP QH C IGPG
EQFKPI HQT C OKVQEJQPFTKCN RTQVGKP KP VJG [GCUVU Saccharomyces cerevisiae CPF Kluy-
veromyces lactis FGURKVG UKOKNCT RTQOQVGT UVTWEVWTGU. /QN /KETQDKQN ü7:õü3ÿõûò
/WNFGT 9, 9KPMNGT 4#, 5EJQNVGP +*ì/, <QPPGXGNF $ì/, &G 9KPFG )*, 5VGGPUOC *;,
)TKXGNN ú# þüùù3ý %GPVTQOGTG RTQOQVGT HCEVQTU þ%2(üý QH VJG [GCUV 5accharomyces
cerevisiae CPF Kluyveromyces lactis CTG HWPEVKQPCNN[ GZEJCPIGCDNG, FGURKVG NQY QXGTCNN
JQOQNQI[. %WTT )GPGV ûø:üùõÿûö7
0IW[GP %, $QNQVKPÿ(WMWJCTC /, 9oUQNQYUMKÿúQWXGN /, (WMWJCTC * þüùùôý 6JG TGURKTCÿ
VQT[ U[UVGO QH Kluyveromyces lactis GUECRGU HTQO *#2û EQPVTQN. )GPG üôû:üü3ÿüüô
ûöö -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

1UKPIC -#, &G *CCP /, %JTKUVKCPUQP 6, 6CDCM *( þüùõûý # PQPCPWENGQVKFG UGSWGPEG KPÿ
XQNXGF KP RTQOQVKQP QH TKDQUQOCN 40# U[PVJGUKU CPF 40# RTKOKPI QH &0# TGRNKECÿ
VKQP KP [GCUV OKVQEJQPFTKC. 0WENGKE #EKFU 4GU üö:7ùù3ÿõööø
1VGTQ ), (GNNQYU ì, úK ;, FG $K\GOQPV 6, &KTCE #/, )WUVCHUUQP %/, ©TFLWOGPVÿ$TQOCIG
*, 6GORUV 2, 5XGLUVTWR ìí þüùùùý ©NQPICVQT, C OWNVKUWDWPKV EQORQPGPV QH C PQXGN
40# RQN[OGTCUG ++ JQNQGP\[OG HQT VTCPUETKRVKQPCN GNQPICVKQP. /QN %GNN 3:üöùÿüüõ
1XGTMCOR -/, $CMMGT $/, 5VGGPUOC *;, 8CP &KLMGP ì2, 2TQPM ì6 þûööûý 6YQ OGEJCÿ
PKUOU HQT QZKFCVKQP QH E[VQUQNKE 0#&2* D[ Kluyveromyces lactis OKVQEJQPFTKC. ;GCUV
üù:õü3ÿõûò
1\KGTÿ-CNQIGTQRQWNQU 1, /CNRGTVW[ #, $Q[GT ì, 6GMCKC (, &WLQP $ þüùùõý 4CPFQO GZRNQÿ
TCVKQP QH VJG Kluyveromyces lactis IGPQOG CPF EQORCTKUQP YKVJ VJCV QH Saccharomy-
ces cerevisiae. 0WENGKE #EKFU 4GU ûø:ôôüüÿôôûò
2GPI ), *QRRGT ì© þûöööý ©XKFGPEG HQT )CN3R'U E[VQRNCUOKE NQECVKQP CPF )CNõöR'U FWCN E[ÿ
VQRNCUOKEÿ PWENGCT NQECVKQP KORNKECVGU PGY OGEJCPKUOU HQT EQPVTQNNKPI )CNòR CEVKXKV[
KP Saccharomyces cerevisiae. /QN %GNN $KQN ûö:ôüòöÿôüòõ
2KUMWT ì þûööüý 1TKIKP QH VJG FWRNKECVGF TGIKQPU KP VJG [GCUV IGPQOGU. 6TGPFU )GPGV
ü7:3öûÿ3ö3
2NCVV #, 4QUU *%, *CPMKP 5, 4GGEG 4ì þûöööý 6JG KPUGTVKQP QH VYQ COKPQ CEKFU KPVQ C VTCPÿ
UETKRVKQPCN KPFWEGT EQPXGTVU KV KPVQ C ICNCEVQMKPCUG. 2TQE 0CVN #ECF 5EK ð 5 # ûööö
/CT ûõ÷ ù7þ7ý:3üôòÿù ù7:3üôòÿ3üôù
2QTTQ &, $KCPEJK //, $TCODKNNC ú, /GPIJKPK 4, $QN\CPK &, %CTTGTC 8, úKGXGPUG ì, úKW
%ú, 4CP\K $/, (TQPVCNK ú, #NDGTIJKPC ú þüùùùý 4GRNCEGOGPV QH C OGVCDQNKE RCVJYC[
HQT NCTIGÿUECNG RTQFWEVKQP QH NCEVKE CEKF HTQO GPIKPGGTGF [GCUVU. #RRN ©PXKTQP /KETQÿ
DKQN øô:òûüüÿòûüô
2TCUCF 4, /KTCNNGU 8ì, $GPKVQ 4/, 5GTTCPQ 4 þüùùùý # RTQRQUCN HQT PQOGPENCVWTG QH CNFGÿ
J[FG FGJ[FTQIGPCUGU KP Saccharomyces cerevisiae CPF EJCTCEVGTK\CVKQP QH VJG UVTGUUÿ
KPFWEKDNG ALD2 CPF ALD3 IGPGU. ;GCUV üô:õûùÿõòû
2TKQT %, (WMWJCTC *, $NCKUQPPGCW ì, 9oUQNQYUMKÿúQWXGN / þüùù3Cý úQYÿCHHKPKV[ INWEQUG
ECTTKGT IGPG LGT1 QH Saccharomyces cerevisiae, C JQOQNQIWG QH VJG Kluyveromyces
lactis RAG1 IGPG. ;GCUV ù:ü373ÿü377
2TKQT %, /COGUUKGT 2, (WMWJCTC *, %JGP îì, 9oUQNQYUMKÿúQWXGN / þüùù3Dý 6JG
JGZQMKPCUG IGPG KU TGSWKTGF HQT VTCPUETKRVKQPCN TGIWNCVKQP QH VJG INWEQUG VTCPURQTVGT
IGPG RAG1 KP Kluyveromyces lactis. /QN %GNN $KQN ü3:3õõûÿ3õõù
2TKQT %, 6K\\CPK ú, (WMWJCTC *, 9oUQNQYUMKÿúQWXGN / þüùùøý RAG3 IGPG CPF VTCPUETKRÿ
VKQPCN TGIWNCVKQP QH VJG R[TWXCVG FGECTDQZ[NCUG IGPG KP Kluyveromyces lactis. /QN /Kÿ
ETQDKQN ûö:7øôÿ77û
4CIPKPK #, (WMWJCTC * þüùõõý /KVQEJQPFTKCN &0# QH VJG [GCUV Kluyveromyces:IWCPKPGÿ
E[VQUKPG TKEJ UGSWGPEG ENWUVGTU. 0WENGKE #EKFU 4GU üø:õò33ÿõòòû
4COKN ©, (TGKTGÿ2KEQU /#, %GTFhP /© þüùùõý %JCTCEVGTK\CVKQP QH RTQOQVGT TGIKQPU KPÿ
XQNXGF KP JKIJ GZRTGUUKQP QH KlCYC1. ©WT ì $KQEJGO ûôø:ø7ÿ7ò
4GGEG 4ì, 2NCVV # þüùù7ý 5KIPCNNKPI CEVKXCVKQP CPF TGRTGUUKQP QH 40# RQN[OGTCUG ++ VTCPÿ
UETKRVKQP KP [GCUV. $KQ©UUC[U üù:üööüÿüöüö
4GNKGPG 4, 5CUPCWMCU - þüùù7ý *GVGTQNQIQWU IGPG GZRTGUUKQP QP VJG NKPGCT RNCUOKFU QH
Kluyveromyces lactis. ;GCUV ü3:5ûû7
4KNG[ /+, &KEMUQP 4% þüùõòý )GPGVKE CPF DKQEJGOKECN EJCTCEVGTK\CVKQP QH VJG ICNCEVQUG
IGPG ENWUVGT KP Kluyveromyces lactis. ì $CEVGTKQN üôõ:7öôÿ7üû
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ûöü

4KNG[ /+, 5TGGMTKUJPC 5, $JCKTK 5, &KEMUQP 4% þüùõ7ý +UQNCVKQP CPF EJCTCEVGTK\CVKQP QH OWÿ
VCPVU KP Kluyveromces lactis FGHGEVKXG KP NCEVQUG VTCPURQTV. /QN )GP )GPGV ûöõ:üòôÿ
üôü
4QEJC 6ú, 2CVGTUQP ), %TKOOKPU -, $Q[F #, 5CY[GT ú, (QVJGTIKNNÿ)KNOQTG ú# þüùùøý
©ZRTGUUKQP CPF UGETGVKQP QH TGEQODKPCPV QXKPG DGVCÿNCEVQINQDWNKP KP Saccharomyces
cerevisiae CPF Kluyveromyces lactis. $KQEJGO ì 3ü3 þ 2V 3ý:ùû7ÿù3û
4QOCPQU /#, $Q[F # þüùõõý # VTCPUETKRVKQPCN DCTTKGT VQ GZRTGUUKQP QH ENQPGF VQZKP IGPGU
QH VJG NKPGCT RNCUOKF Mü QH Kluyveromyces lactis:GXKFGPEG VJCV PCVKXG Mü JCU PQXGN
RTQOQVGTU. 0WENGKE #EKFU 4GU üø:7333ÿ73ôö
4WDKQÿ6GZGKTC /, #TGXCNQÿ4QFTKIWG\ /, úGSWGTKEC ìú, 2QNCKPC ì þûööüý úCEVQUG WVKNK\CVKQP
D[ Saccharomyces cerevisiae UVTCKPU GZRTGUUKPI Kluyveromyces lactis LAC IGPGU. ì
$KQVGEJPQN õò:ù7ÿüöø
4W\\K /, $TGWPKI -&, (KEEC #), *QNNGPDGTI %2 þüùõ7ý 2QUKVKXG TGIWNCVKQP QH VJG ¾ÿ
ICNCEVQUKFCUG IGPG HTQO Kluyveromyces lactis KU OGFKCVGF D[ CP WRUVTGCO CEVKXCVKQP
UKVG VJCV UJQYU JQOQNQI[ VQ VJG GAL WRUVTGCO CEVKXCVKQP UKVG QH Saccharomyces cere-
visiae. /QN %GNN $KQN 7:ùùûÿùù7
5CFQYUMK +, %QUCV %, &JCPCYCPUC 4 þüùùøý 2JQURJQT[NCVKQP QH )CNòR CV C UKPING %ÿ
VGTOKPCN TGUKFWG KU PGEGUUCT[ HQT ICNCEVQUGÿKPFWEKDNG VTCPUETKRVKQP. /QN %GNN $KQN
üø:òõ7ùÿòõõ7
5CNKQNC /, /C\\QPK %, 5QNKOCPFQ 0, %TKUC #, (CNEQPG %, ìWPI ), (NGGT 4 þüùùùý ðUG QH
VJG KlADH4 RTQOQVGT HQT GVJCPQNÿFGRGPFGPV RTQFWEVKQP QH TGEQODKPCPV JWOCP UGTWO
CNDWOKP KP Kluyveromyces lactis. #RRN ©PXKTQPO /KETQDKQN øô:ô3ÿøö
5CNOGTQP ì/, ìQJPUVQP 5# þüùõøý #PCN[UKU QH VJG Kluyveromyces lactis RQUKVKXG TGIWNCVQT[
IGPG LAC9 TGXGCNU HWPEVKQPCN JQOQNQI[ VQ, DWV UGSWGPEG FKXGTIGPEG HTQO, VJG Sac-
charomyces cerevisiae GAL4 IGPG. 0WENGKE #EKFU 4GU üò:77ø7ÿ77õü
5CVQ 6, úQRG\ /%, 5WIKQMC 5, ìKICOK ;, $CMGT *8, ðGOWTC * þüùùùý 6JG ©ÿDQZ &0#
DKPFKPI RTQVGKP 5IEüR UWRRTGUUGU VJG gcr2 OWVCVKQP, YJKEJ KU KPXQNXGF KP VTCPUETKRÿ
VKQPCN CEVKXCVKQP QH IN[EQN[VKE IGPGU KP Saccharomyces cerevisiae. (©$5 úGVV òø3:3ö7ÿ
3üü
5EJCHHTCVJ 4, $TGWPKI -& þûöööý )GPGVKEU CPF OQNGEWNCT RJ[UKQNQI[ QH VJG [GCUV Kluy-
veromyces lactis. (WPICN )GPGV $KQN 3ö:ü73ÿüùö
5EJCHHTCVJ 4, /GCEQEM 2# þûööüý #P 55$ GPEQFGF D[ CPF QRGTCVKPI QP NKPGCT MKNNGT RNCUÿ
OKFU HTQO Kluyveromyces lactis. ;GCUV üõ:üû3ùÿüûò7
5EJCHHTCVJ 4, /GKPJCTFV (, /GCEQEM 2# þüùù7ý 14(7 QH [GCUV RNCUOKF R)-úû:CPCN[UKU QH
IGPG GZRTGUUKQP KP XKXQ. %WTT )GPGV 3ü:üùöÿüùû
5EJCHHTCVJ 4, /GKPJCTFV (, /GCEQEM 2# þüùùùý )GPGVKE OCPKRWNCVKQP QH Kluyveromyces
lactis NKPGCT &0# RNCUOKFU:IGPG VCTIGVKPI CPF RNCUOKF UJWHHNGU. (©/5 /KETQDKQN úGVV
ü7õ:ûöüÿûüö
5EJCHHTCVJ 4, 5QQPF 5/, /GCEQEM 2# þüùùôý 6JG &0# CPF 40# RQN[OGTCUG IGPGU QH
[GCUV RNCUOKF R)-úû CTG GUUGPVKCN NQEK HQT RNCUOKF KPVGITKV[ CPF OCKPVGPCPEG. /KETQÿ
DKQNQI[ üòü þ 2V üöý:ûôùüÿûôùù
5EJKEMGN ì, *GNOKI %, /GKPJCTFV ( þüùùøý Kluyveromyces lactis MKNNGT U[UVGO:CPCN[UKU QH
E[VQRNCUOKE RTQOQVGTU QH VJG NKPGCT RNCUOKFU. 0WENGKE #EKFU 4GU ûò:üõ7ùÿüõõø
5GQKIJG %, 9QNHG -* þüùùùý ;GCUV IGPQOG GXQNWVKQP KP VJG RQUVÿIGPQOG GTC. %WTT 1RKP
/KETQDKQN û:ôòõÿôôò
5QWEKGV ì, #KING /, #TVKIWGPCXG (, $NCPFKP ), $QNQVKPÿ(WMWJCTC /, $QP ©, $TQVVKGT 2,
%CUCTGIQNC 5, FG /QPVKIP[ ì, &WLQP $, &WTTGPU 2, )CKNNCTFKP %, úGRKPING #, úNQTGPVG
$, /CNRGTVW[ #, 0GWXGINKUG %, 1\KGTÿ-CNQIGTQRQWNQU 1, 2QVKGT 5, 5CWTKP 9, 6GMCKC (,
ûöû -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

6QHHCPQÿ0KQEJG %, 9GUQNQYUMKÿúQWXGN /, 9KPEMGT 2, 9GKUUGPDCEJ ì þûöööý )Gÿ

PQOKE GZRNQTCVKQP QH VJG JGOKCUEQO[EGVQWU [GCUVU:ü. # UGV QH [GCUV URGEKGU HQT OQÿ
NGEWNCT GXQNWVKQP UVWFKGU. (©$5 úGVV òõ7:3ÿüû
5TGGMTKUJPC -, &KEMUQP 4% þüùõôý %QPUVTWEVKQP QH UVTCKPU QH Saccharomyces cerevisiae
VJCV ITQY QP NCEVQUG. 2TQE 0CVN #ECF 5EK ð5# õû:7ùöùÿ7ùü3
5VCTM /ì, $Q[F # þüùõøý 6JG MKNNGT VQZKP QH Kluyveromyces lactis:%JCTCEVGTK\CVKQP QH VJG
VQZKP UWDWPKVU CPF KFGPVKHKECVKQP QH VJG IGPGU YJKEJ GPEQFG VJGO. ©/$1 ì ô:üùùôÿ
ûööû
5VCTM /ì, $Q[F #, /KNGJCO #ì, 4QOCPQU /# þüùùöý 6JG RNCUOKFÿGPEQFGF MKNNGT U[UVGO
QH Kluyveromyces lactis:C TGXKGY. ;GCUV ø:üÿûù
5VGGPUOC *;, FG ìQPIJ (%/, úKPPGMCOR / þüùõõý 6JG WUG QH GNGEVTQRJQTGVKE MCT[QV[RGU
KP VJG ENCUUKHKECVKQP QH [GCUVU:Kluyveromyces marxianus CPF K.lactis. %WTT )GPGV
üò:3üüÿ3ü7
5VGGPUOC *;, 6GT úKPFG ìì/ þûööüý 2NCUOKFU YKVJ VJG %TGÿTGEQODKPCUG CPF VJG nat
OCTMGT, UWKVCDNG HQT WUG KP RTQVQVTQRJKE UVTCKPU QH Saccharomyces cerevisiae CPF Kluy-
veromyces lactis. ;GCUV üõ:òøùÿò7û
5WDsM ì, -QNCTQX ì, -QXhE ú þüù7òý #PCGTQDKE ITQYVJ HQTOCVKQP QH TGURKTCVKQPÿFGHKEKGPV
OWVCPVU QH XCTKQWU URGEKGU QH [GCUV. (©$5 úGVV òô:ûø3ÿûøø
5XGLUVTWR ìí þûööûý %JTQOCVKP GNQPICVKQP HCEVQTU. %WTT 1RKP )GPGV &GX üû:üôøÿüøü
5YGPPGP &, 2CWN /(, 8GTPKU ú, $GEMGTKEJ ì/, (QWTPKGT #, )CKNNCTFKP % þûööûý 5GETGVKQP
QH CEVKXG CPVKÿ4CU UKPINGÿEJCKP (X CPVKDQF[ D[ VJG [GCUVU Yarrowia lipolytica CPF
Kluyveromyces lactis. /KETQDKQNQI[ üòõ:òüÿôö
5YKPMGNU $9, XCP 1Q[GP #ì, $QPGMCOR (ì þüùù3ý 6JG [GCUV Kluyveromyces lactis CU CP
GHHKEKGPV JQUV HQT JGVGTQNQIQWU IGPG GZRTGUUKQP. #PVQPKG 8CP úGGWYGPJQGM øò:üõ7ÿ
ûöü
6CMGFC /, *KTCKUJK *, 6CMGUCMQ 6, 6CPCUG 5, )WPIG 0 þüùùøý 6JG VGTOKPCN RTQVGKP QH VJG
NKPGCT &0# RNCUOKF R)-úû UJCTGU CP 0ÿ VGTOKPCN FQOCKP QH VJG RNCUOKFÿGPEQFGF
&0# RQN[OGTCUG. ;GCUV üû:ûòüÿûòø
6GT úKPFG ìì/, úKCPI *, &CXKU 49, 5VGGPUOC *;, 8CP &KLMGP ì2, 2TQPM ì6 þüùùùý )Gÿ
PQOGÿYKFG VTCPUETKRVKQPCN CPCN[UKU QH CGTQDKE CPF CPCGTQDKE EJGOQUVCV EWNVWTGU QH
Saccharomyces cerevisiae. ì $CEVGTKQN üõü:7òöùÿ7òü3
6GT úKPFG ìì/, 5VGGPUOC *; þûöö3ý 6TCPUETKRVKQPCN TGIWNCVKQP QH YML083c WPFGT CGTQDKE
CPF CPCGTQDKE EQPFKVKQPU. ;GCUV ûö:ò3ùÿòôò
6K\\CPK ú, /GCEQEM 2, (TQPVCNK ú, 9oUQNQYUMKÿúQWXGN / þüùùõý 6JG RAG3 IGPG QH Kluy-
veromyces lactis KU KPXQNXGF KP VJG VTCPUETKRVKQPCN TGIWNCVKQP QH IGPGU EQFKPI HQT GPÿ
\[OGU KORNKECVGF KP R[TWXCVG WVKNK\CVKQP CPF IGPGU QH VJG DKQU[PVJGUKU QH VJKCOKPG R[ÿ
TQRJQURJCVG. (©/5 /KETQDKQN úGVV üøõ:ûôÿ3ö
6QMWPCIC /, -CYCOWTC #, *KUJKPWOC ( þüùõùý ©ZRTGUUKQP QH R)-ú MKNNGT ûõ- UWDWPKV KP
Saccharomyces cerevisiae:KFGPVKHKECVKQP QH ûõ- UWDWPKV CU C MKNNGT RTQVGKP. 0WENGKE #Eÿ
KFU 4GU ü7:3ò3ôÿ3òòø
6QMWPCIC /, 9CFC 0, *KUJKPWOC ( þüùõ7ý ©ZRTGUUKQP CPF KFGPVKHKECVKQP QH KOOWPKV[ FGÿ
VGTOKPCPVU QP NKPGCT &0# MKNNGT RNCUOKFU R)-úü CPF R)-úû KP Kluyveromyces lactis.
0WENGKE #EKFU 4GU üô:üö3üÿüöòø
6QOOCUKPQ / þüùùüý -KNNGT U[UVGO QH Kluyveromyces lactis:6JG QRGP TGCFKPI HTCOG üö QH
VJG R)-üû RNCUOKF GPEQFGU C RWVCVKXG &0# DKPFKPI RTQVGKP. ;GCUV 7:ûòôÿûôû
6QOOCUKPQ /, 4KEEK 5, )CNGQVVK %ú þüùõõý )GPQOG QTICPK\CVKQP QH VJG MKNNGT RNCUOKF
R)-üû HTQO Kluyveromyces lactis. 0WENGKE #EKFU 4GU üø:ôõø3ÿôõ7õ
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ûö3

6To\oIWGV 8, <GOCP +, &CXKF %, úCWSWKP )ì/, -QNCTQX ì þüùùùý ©ZRTGUUKQP QH VJG

#&2ñ#62 ECTTKGT GPEQFKPI IGPGU KP CGTQDKE [GCUV÷ RJGPQV[RG QH CP #&2ñ#62 ECTTKGT
FGNGVKQP OWVCPV QH Schizosaccharomyces pombe. $KQEJKO $KQRJ[U #EVC üòüö:ûûùÿû3ø
ðEEGNNGVVK &, &G ìCEQ #, (CTKPC (, /CPEKPK 2, #WIWUVKÿ6QEEQ ), $KCIKQPK 5, 2CNNGUEJK %
þûööûý %GNN UWTHCEG GZRTGUUKQP QH C )2+ÿCPEJQTGF HQTO QH OQWUG CEGV[NEJQNKPGUVGTCUG
KP Klpmr1&GNVC EGNNU QH Kluyveromyces lactis. $KQEJGO $KQRJ[U 4GU %QOOWP
ûùõ:ôôùÿôøô
ðEEGNNGVVK &, 2CEGNNK 8, /CPEKPK 2, 2CNNGUEJK % þûöööý vga OWVCPVU QH Kluyveromyces lactis
UJQY EGNN KPVGITKV[ FGHGEVU. ;GCUV üø:üüøüÿüü7ü
ðGOWTC *, ìKICOK ; þüùùûý 4QNG QH )%4û KP VTCPUETKRVKQPCN CEVKXCVKQP QH [GCUV IN[EQN[VKE
GP\[OGU. /QN %GNN $KQN üû:3õ3òÿ3õòû
ðGOWTC *, -QUJKQ /, +PQWG ;, úQRG\ /%, $CMGT *8 þüùù7ý 6JG TQNG QH )ETüR KP VJG
VTCPUETKRVKQPCN CEVKXCVKQP QH IN[EQN[VKE IGPGU KP [GCUV Saccharomyces cerevisiae. )Gÿ
PGVKEU üò7:ôûüÿô3û
8CP FGP $GTI ì#, 8CP FGT úCMGP -ì, XCP 1Q[GP #ì, 4GPPKGTU 6%, 4KGVXGNF -, 5EJCCR #,
$TCMG #ì, $KUJQR 4ì, 5EJWNV\ -, /Q[GT & þüùùöý Kluyveromyces CU C JQUV HQT JGVÿ
GTQNQIQWU IGPG GZRTGUUKQP:GZRTGUUKQP CPF UGETGVKQP QH RTQEJ[OQUKP. $KQVGEJPQNQI[ þ0
; ý õ:ü3ôÿü3ù
8CP FGP $GTI /#, 5VGGPUOC *; þüùùôý ACS2, C Saccharomyces cerevisiae IGPG GPEQFKPI
CEGV[NÿEQGP\[OG # U[PVJGVCUG, GUUGPVKCN HQT ITQYVJ QP INWEQUG. ©WT ì $KQEJGO
û3ü:7öòÿ7ü3
8CWIJCPÿ/CTVKPK #, /CTVKPK #, %CTFKPCNK ) þüùù3ý ©NGEVTQRJQTGVKE MCT[QV[RKPI CU C VCZQÿ
PQOKE VQQN KP VJG IGPWU Saccharomyces. #PVQPKG 8CP úGGWYGPJQGM ø3:üòôÿüôø
XCP ðTM *, 2QUVOC ©, 5EJGHHGTU 9#, 8CP &KLMGP ì2 þüùõùý )NWEQUG VTCPURQTV KP %TCDVTGGÿ
RQUKVKXG CPF %TCDVTGGÿPGICVKXG [GCUVU. ì )GP /KETQDKQN ü3ô:û3ùùÿûòöø
8KQNC #/, )CNGQVVK %ú, )QHHTKPK 2, (KECTGNNK #, (GTTGTQ + þüùùôý # Kluyveromyces lactis
IGPG JQOQNQIWG VQ AAC2 EQORNGOGPVU VJG Saccharomyces cerevisiae op1 OWVCVKQP.
%WTT )GPGV û7:ûûùÿû33
8KQNC #/, úQFK 6, (GTTGTQ + þüùùùý # Klaac PWNN OWVCPV QH Kluyveromyces lactis KU EQOÿ
RNGOGPVGF D[ C UKPING EQR[ QH VJG Saccharomyces cerevisia AAC1 IGPG. %WTT )GPGV
3ø:ûùÿ3ø
8KUUGT 9, 5EJGHHGTU 9#, $CVGPDWTIÿXCP FGT 8GIVG 9*, 8CP &KLMGP ì2 þüùùöý 1Z[IGP TGÿ
SWKTGOGPVU QH [GCUVU. #RRN ©PXKTQPO /KETQDKQN ôø:37õôÿ37ùû
9GKTKEJ ì, )QHHTKPK 2, -WIGT 2, (GTTGTQ +, $TGWPKI -& þüùù7ý +PHNWGPEG QH OWVCVKQPU KP
JGZQUGÿVTCPURQTVGT IGPGU QP INWEQUG TGRTGUUKQP KP Kluyveromyces lactis. ©WT ì $KQÿ
EJGO ûòù:ûòõÿûô7
9GP\GN 6ì, 8CP FGP $GTI /#, 8KUUGT 9, 8CP FGP $GTI ì#, 5VGGPUOC *; þüùùûý %JCTCEÿ
VGTK\CVKQP QH Saccharomyces cerevisiae OWVCPVU NCEMKPI VJG ©ü½ UWDWPKV QH VJG R[TWÿ
XCVG FGJ[FTQIGPCUG EQORNGZ. ©WT ì $KQEJGO ûöù:øù7ÿ7öô
9oUQNQYUMKÿúQWXGN /, $TGWPKI -&, (WMWJCTC * þüùùøý Kluyveromyces lactis. +P:9QNH -
þGFý 0QPÿ%QPXGPVKQPCN ;GCUVU KP $KQVGEJPQNQI[. 5RTKPIGTÿ8GTNCI, *GKFGNDGTI
9oUQNQYUMKÿúQWXGN /, (WMWJCTC * þüùùôý # OCR QH VJG Kluyveromyces lactis IGPQOG.
;GCUV üü:ûüüÿûüõ
9oUQNQYUMKÿúQWXGN /, )QHHTKPK 2, (GTTGTQ +, (WMWJCTC * þüùùûDý )NWEQUG VTCPURQTV KP VJG
[GCUV Kluyveromyces lactis. + 2TQRGTVKGU QH CP KPFWEKDNG NQYÿCHHKPKV[ INWEQUG VTCPUÿ
RQTVGT IGPG. /QN )GP )GPGV û33:õùÿùø
ûöò -CTKP &. $TGWPKI CPF *. ;FG 5VGGPUOC

9oUQNQYUMKÿúQWXGN /, 2TKQT %, $QTPGESWG &, (WMWJCTC * þüùùûCý 4CIÿOWVCVKQPU KPÿ

XQNXGF KP INWEQUG OGVCDQNKUO KP [GCUV:KUQNCVKQP CPF IGPGVKE EJCTCEVGTK\CVKQP. ;GCUV
õ:7üüÿ7üù
9KNUQP &9, /GCEQEM 2# þüùõõý ©ZVTCPWENGCT IGPG GZRTGUUKQP KP [GCUV:GXKFGPEG HQT C
RNCUOKFÿGPEQFGF 40# RQN[OGTCUG QH WPKSWG UVTWEVWTG. 0WENGKE #EKFU 4GU üø:õöù7ÿ
õüüû
9KPMNGT ##, )QGFGIGDWTG 4*, <QPPGXGNF $ì, 5VGGPUOC *;, *QQ[MCCU 2ì þûöööCý +UQNCÿ
VKQP CPF RCTVKCN EJCTCEVGTK\CVKQP QH VJG Kluyveromyces lactis JQOQNQIWG QH 5-2ü. %WTT
)GPGV 3õ:õÿüø
9KPMNGT ##, -QTUVCPLG 4, <QPPGXGNF $ì, *QQ[MCCU 2ì, 5VGGPUOC *; þûöööDý +UQNCVKQP
CPF EJCTCEVGTK\CVKQP QH -+ð$2û, C WDKSWKVKP J[FTQNCUG IGPG QH Kluyveromyces lactis
VJCV ECP UWRRTGUU C VUÿOWVCVKQP KP %$(û, C IGPG GPEQFKPI C EGPVTQOGTKE RTQVGKP QH
Saccharomyces cerevisiae. %WTT )GPGV 3õ:ü7ÿûû
9KPMNGT )5, 2GVTCMKU 6), ©VJGNDGTI 5, 6QMWPCIC /, ©TFLWOGPVÿ$TQOCIG *, 6GORUV 2,
5XGLUVTWR ìí þûööüý 40# RQN[OGTCUG ++ GNQPICVQT JQNQGP\[OG KU EQORQUGF QH VYQ
FKUETGVG UWDEQORNGZGU. ì $KQN %JGO û7ø:3û7ò3ÿ3û7òù
9QNH,-.÷ $TGWPKI,-.&.÷ $CTVJ,).þ©FU.ý þûöö3ý. 0QPÿ%QPXGPVKQPCN ;GCUVU KP )GPGVÿ
KEU,$KQEJGOKUVT[ CPF $KQVGEJPQNQI[. *GKFGNDGTI, 5RTKPIGTÿ8GTNCI.
9QNHG -*, 5JKGNFU &% þüùù7ý /QNGEWNCT GXKFGPEG HQT CP CPEKGPV FWRNKECVKQP QH VJG GPVKTG
[GCUV IGPQOG. 0CVWTG 3õ7:7öõÿ7ü3
9TC[ ú8ì, 9KVVG /9, &KEMUQP 4%, 4KNG[ /+ þüùõ7ý %JCTCEVGTK\CVKQP QH C RQUKVKXG TGIWNCÿ
VQT[ IGPG, LAC9, VJCV EQPVTQNU KPFWEVKQP QH VJG NCEVQUGÿICNCEVQUG TGIWNQP QH Kluyvero-
myces lactis:UVTWEVWTCN CPF HWPEVKQPCN TGNCVKQPUJKRU VQ GAL4 QH Saccharomyces cere-
visiae. /QN %GNN $KQN 7:üüüüÿüüûü
;CR 0#, FG $CTTQU ú/, úCPITKFIG 2, *GPUEJMG 2# þûöööý 6JG KPEKFGPEG QH MKNNGT CEVKXKV[
QH PQPÿSaccharomyces yeasts VQYCTFU KPFKIGPQWU [GCUV URGEKGU QH ITCRG OWUV:RQVGPVKCN
CRRNKECVKQP KP YKPG HGTOGPVCVKQP. ì #RRN /KETQDKQN õù:3õüÿ3õù
;QUJKFC #, 4\JGVUM[ #, *UW ú%, %JCPI % þüùùõý *WOCP CNFGJ[FG FGJ[FTQIGPCUG IGPG
HCOKN[. ©WT ì.$KQEJGO ûôü:ôòùÿôô7
;WCP ;1, 5VTQMG +ú, (KGNFU 5 þüùù3ý %QWRNKPI QH EGNN KFGPVKV[ VQ UKIPCN TGURQPUG KP
[GCUV:KPVGTCEVKQP DGVYGGP VJG CNRJC ü CPF STE12 RTQVGKPU. )GPGU &GX 7:üôõòÿüôù7
<CEJCTKCG 9, $TGWPKI -& þüùù3ý ©ZRTGUUKQP QH VJG VTCPUETKRVKQPCN CEVKXCVQT ú#%ù
þ-N)#úòý KP Kluyveromyces lactis KU EQPVTQNNGF D[ CWVQTGIWNCVKQP. /QN %GNN $KQN
ü3:3öôõÿ3öøø
<CTQT +, /CTEWU (, /Q[GT &ú, 6WPI ì, 5JWUVGT ì4 þüùù3ý (TWEVQUGÿü,øÿDKURJQURJCVCUG QH
VJG [GCUV Kluyveromyces lactis. ©WT ì $KQEJGO ûüû:üù3ÿüùù
<GGOCP #ÿ/, -W[RGT /, 2TQPM ì6, 8CP &KLMGP ì2, 5VGGPUOC *; þûöööý 4GIWNCVKQP QH R[ÿ
TWXCVG OGVCDQNKUO KP EJGOQUVCV EWNVWTGU QH Kluyveromyces lactis %$5 û3ôù. ;GCUV
üø:øüüÿøûö
<GGOCP #ÿ/, úWVVKM /#*, 2TQPM ì6, 8CP &KLMGP ì2, 5VGGPUOC *; þüùùùý +ORCKTGF
ITQYVJ QP INWEQUG QH C R[TWXCVG FGJ[FTQIGPCUGÿPGICVKXG OWVCPV QH Kluyveromyces
lactis KU FWG VQ C NKOKVCVKQP KP OKVQEJQPFTKCN CEGV[NÿEQGP\[OG # WRVCMG. (©/5 /KETQÿ
DKQN úGVV ü77:û3ÿûõ
<GGOCP #ÿ/, úWVVKM /#*, 6JKGNG %, 8CP &KLMGP ì2, 2TQPM ì6, 5VGGPUOC *; þüùùõý +PCEÿ
VKXCVKQP QH VJG Kluyveromyces lactis KlPDA1 IGPG NGCFU VQ NQUU QH R[TWXCVG FGJ[FTQÿ
IGPCUG CEVKXKV[, KORCKTU ITQYVJ QP INWEQUG CPF VTKIIGTU CNEQJQNKE HGTOGPVCVKQP. /KETQÿ
DKQNQI[ üòò:3ò37ÿ3òòø
 ø Kluyveromyces lactis: IGPGVKEU, RJ[UKQNQI[, CPF CRRNKECVKQP ûöô

<GGOCP #ÿ/, 5VGGPUOC *; þûöö3ý 6JG CEGV[N EQÿGP\[OG # U[PVJGVCUG IGPGU QH Kluy-
veromyces lactis. ;GCUV ûö:ü3ÿû3
<GPI î, &GOKPQHH ì, 5CPVCPIGNQ )/ þüùù7ý 5RGEKCNK\GF 4CRüRñ)ETüR VTCPUETKRVKQPCN CEVKÿ
XCVKQP VJTQWIJ )ETüR &0# EQPVCEVU TGSWKTGU )ETûR, CU FQGU J[RGTRJQURJQT[NCVKQP QH
)ETüR. )GPGVKEU üò7:òù3ÿôöô
<GPMG (, <CEJCTKCG 9, úWPMGU #, $TGWPKI -& þüùù3ý )CNõö RTQVGKPU QH Kluyveromyces
lactis CPF Saccharomyces cerevisiae CTG JKIJN[ EQPUGTXGF DWV EQPVTKDWVG FKHHGTGPVN[ VQ
INWEQUG TGRTGUUKQP QH VJG ICNCEVQUG TGIWNQP. /QN %GNN $KQN ü3:7ôøøÿ7ô7ø
<GPMG (6, ©PIGNU 4, 8QNNGPDTQKEJ 8, /G[GT ì, *QNNGPDGTI %2, $TGWPKI -& þüùùøý #EVKXCÿ
VKQP QH )CNòR D[ ICNCEVQUGÿFGRGPFGPV KPVGTCEVKQP QH ICNCEVQMKPCUG CPF )CNõöR. 5EKGPEG
û7û:üøøûÿüøøô
<GPMG (6, -CRR ú, $TGWPKI -& þüùùùý 4GIWNCVGF RJQURJQT[NCVKQP QH VJG )CNòR KPJKDKVQT
)CNõöR QH Kluyveromyces lactis TGXGCNGF D[ OWVCVKQPCN CPCN[UKU. $KQN %JGOKUVT[
3õö:òüùÿò3ö