Section VI

Photosynthesis in Lower and

Monocellular Plants

© 2005 by Taylor & Francis Group, LLC

 Regulation of Phycobilisome
23 Biosynthesis and Degradation in
Cyanobacteria
Johannes Geiselmann
Adaptation et Pathogénie des Microorganismes, Université Joseph Fourier

Jean Houmard
Organismes Photosynthétiques et Environnement, Ecole Normale Supérieure

Benoiˆ
t Schoefs
Dynamique Vacuolaire et Réponses aux Stress de l’Environnement,
UMR CNRS 5184/INRA 1088/Université de Bourgogne Plante-Microbe-Environnement,
Université de Bourgogne à Dijon

CONTENTS

I. Introduction
II. Pigment, Polypeptide Organization, and Functioning of the Phycobilisomes
III. Pigment Biosynthesis
IV. Genome Organization
V. Transcriptional Regulations Induced by Environmental Changes:
A Complex Intricate Network
A. Nutrient Availability
B. Stress by Light
VI. Regulatory Logic
A. Control of PBS Synthesis and Degradation
B. The Key Regulatory Proteins
C. Common Themes of Regulation
References

I. INTRODUCTION I and PS II), most cyanobacteria harvest light through

Extant cyanobacteria derive from the oldest oxygen-
evolving photosynthetic organisms that appeared on
Earth some billion years ago. Their photosynthetic
apparatus is very similar to the one of green plants
and was at its origin. Indeed the chloroplasts of green
plants and algae all derive from a unique endosymbiotic
event that occured between a cyanobacterial ancestor
and a primitive eukaryotic cell (Ref. [1] and references
therein). Although oxygen-evolving photosynthesis is
achieved by the same mechanism, differences exist in
the light-harvesting apparatus between phylogenetic
groups. Instead of the integral membrane light-harvest-
ing complexes that surround photosystems I and II (PS
an extrinsic membrane-anchored, water-soluble multi-
protein assembly, the phycobilisome (PBS). This struc-
ture transfers the light energy to the underlying PSs [2].
PS II uses the harvested energy to create a charge sep-
aration at the level of special chlorophyll (Chl) mol-
ecules. The electron is then transferred to PS I through
the chain of electron transporters while the electrical
neutrality of the special Chl molecules is restored by the
transfer of one electron coming from the oxidation of a
water molecule.
Survival of free-living organisms in a changing
environment relies upon their capacity to modulate
their cellular metabolism according to the external
conditions. As energy production relies on photosyn-

© 2005 by Taylor & Francis Group, LLC

thesis, it clearly appears that the effective absorption
of light by PBSs is a critical step in the photosynthetic
process and thus for the physiology of the photosyn-
thetic organisms. Light flux to the PSs must therefore
be strongly regulated. In cyanobacteria, most of this
regulation occurs by controlling the transcription of
the genes coding for the PBS components. The pur-
pose of this contribution is to: (i) review the literature
dealing with the regulation of PBS biosynthesis and
degradation; and (ii) present models for the biochem-
ical and regulatory networks involved in this process.
The organization of the cyanobacterial cells, their
photosynthetic apparatus, as well as their physiology
may differ between taxons (even at the species level) [3–
5]. Responses specific and adapted to changes in the
environmental parameters have been described for
strains able to differentiate, fix atmospheric dinitrogen
and perform complementary chromatic adaptation
(e.g., [6,7]). Extensive structural and functional analyses
of PBS have been performed, and different shapes have
been observed. We will focus this chapter on the most
common hemidiscoidal PBS that consists of a central
tricylindrical core from which six rods radiate [2].
II. PIGMENT, POLYPEPTIDE
ORGANIZATION, AND FUNCTIONING
OF THE PHYCOBILISOMES
PBSs form an ordered spatial arrangement, which
covers the outer surface of the photosynthetic mem-
branes. In electron micrographs, PBSs generally ap-
pear as being made up of two discrete subdomains:
the ‘‘core’’ and the ‘‘peripheral rods’’. In a front view,
the core presents itself as three stacked cylinders that
form a triangle (or, for a few strains, only as two
stacked cylinders arranged side-by-side; reviewed in
Ref. [4]). The composition and length of the rods
depend on cell growth conditions. For the hemidis-
coidal PBSs, both the core cylinders and the rods are
composed of stacked disks, connected by the so-called
linker polypeptides (reviewed in Ref. [4]). The poly-
peptides required for the building up of functional
PBSs or associated with them may be grouped into
three classes (Table 23.1):
Phycobiliproteins (PB): These proteins carry
open tetrapyrrolic pigments and represent
about 85% of the total PBS proteins. Typically,
cyanobacteria contain two main PBs, namely
phycocyanin (PC), which forms the rods and
allophycocyanin (AP), which forms the core
[2]. Some strains may additionally possess, as
part of the rods, either a second type of PC,
phycoerythrin (PE) or phycoerythrocyanin
© 2005 by Taylor & Francis Group, LLC
(PEC). Most PBSs are heteromonomers com-
posed of equimolar amounts of a and b sub-
units. The a and b subunits of AP and the a
subunit of PC and PEC bind one chromophore
molecule whereas the b subunit of PC and PEC,
as well as the a subunit of PE bind two chro-
mophore molecules, three chromophores being
bound to the b subunit of PE (Table 23.1) [2,8].
Some marine strains contain yet another type of
PE that carries PUB chromophores [2]. The a
and b subunits assemble to form either trimers
in the core or hexamers (ab)6 in the rods. The
most recent refined structure reported for a PB
is the one of c-PC from Thermosynechococcus
vulcanus, solved to 1.6 Å resolution [9].
Linker polypeptides: They account for approxi-
mately 10 to 20% of the total PBS proteins.
The generally accepted nomenclature uses the
abbreviation LXY, with X referring to the loca-
tion of the linker within the structure (C for
core, R for rod, and M for membrane), and Y
to its apparent molecular mass (if it is a num-
ber) or the PB with which it is associated (if
letters, PC, PE, or PEC). Most of the linker
polypeptides are nonpigmented, exceptions
being: (i) the largest one (LCM), which always
carries a phycocyanobilin and serves as terminal
energy acceptor for the PBS; and (ii) the re-
cently discovered PE-associated rod linkers
of the marine Synechococcus sp. WH8102 (F.
Partensky, personal communication). The lin-
ker polypeptides have different functions: they
are involved in the association of the PB trimers
and they modify the absorption properties of
the PBSs and thus have to perform a unidirec-
tional transfer of the excitation energy within
the PBS structure [2]. The above mentioned
LCM, besides its role as terminal energy ac-
ceptor, plays a key role in the assembly of the
PBS core. It has been shown that it is the scaf-
fold onto which AP subunits assemble, its size
determining the shape of the core [10,11]. Most
of the linkers induce a face-to-face aggregation
of trimers and tail-to-tail joining of hexamers in
the peripheral rods. It has been suggested that
the linker proteins occupy positions running
through the internal cavities of the disks. The
small LC has been crystallized with AP trimers
and the structure showed it lying within the
cavity, in contact with two AP ab monomers
[12]. On the basis of crystallographic data and
calculation, it has been proposed that a special
PC isoform, together with specific linkers (LRC),
make the contact between the PC rods and the
AP core in T. vulcanus [13]. Models have been
TABLE 23.1
Phycobilisome Components and Associated Proteins

Protein Pigment Function Gene Names

Phycobiliproteins
aAP-B 1 PCB Core terminal energy acceptor apcD
aAP 1 PCB Allophycocyanin a subunit apcA
bAP 1 PCB Allophycocyanin b subunit apcB
b18.3 1 PCB Allophycocyanin b-type subunit apcF
aPC 1 PCB Phycocyanin a subunit cpcA
bPC 2 PCB Phycocyanin b subunit cpcB
aPE 2 PEB Phycoerythrin a subunit cpeA
bPE 3 PEB Phycoerythrin b subunit cpeB
aPEC 1 PCB Phycoerythrocyanin a subunit pecA
bPEC 1 PCB þ 1 PXB Phycoerythrocyanin b subunit pecB

Linker polypeptides
LCM 1 PCB Large core linker with a PB domain apcE
acting as terminal energy acceptor
LC None Small core linker apcC
LRC None Core–rod linker cpcG
LRPC None Rod linker for PC cpcC or cpcH or cpcI
LR10 None Small rod linker cpcD
LRPE None Rod linker for PE cpeC or cpeD or cpeE
LRPEC None Rod linker for PEC pecC

Associated proteins
CpcE None a Subunit of the phycocyanobilin lyase cpcE
CpcF None b Subunit of the phycocyanobilin lyase cpcF
CpeY None Putative a subunit of the phycoerythrobilin lyase cpeY
CpeZ None Putative b subunit of the phycocyanobilin lyase cpcZ
PecE None a Subunit of the phycoerythrocyanobilin lyase pecE
PecE None b Subunit of the phycoerythrocyanobilin lyase pecF
PcyA None Phycocyanobilin:ferredoxin oxidoreductase pcyA
NblA None Polypeptide involved in PBS degradation nblA
FNR or PetH None Ferredoxin-NADP oxidoreductase petH

proposed to explain the close to 100% transfer
of excitation energy all along the supramolecu-
lar structure: first from the distal to the prox-
imal hexamer within the rods [2,14], from the
rods to the core, and then to the reaction cen-
ters that are embedded into the thylakoid mem-
branes (for a model of the interaction between
AP and PS II [15].
PBS-associated proteins: Although tetrapyrroles
can spontaneously form adducts with PB apo-
proteins, it has been shown that specific lyases
are necessary for the attachment of phycocya-
nobilin to the a subunits of PC [16]. Similarly,
another lyase is required to produce holo-PEC
from the apo-PEC a subunit [17]. Genes shar-
ing similarities with the ones that code for these
lyases have been reported, and their products
would catalyze the covalent attachment of phy-
coerythrobilin to the apo-PE a subunit [18]. All
of these lyases are heterodimeric enzymes. On
the other hand, the copurification of the
ferredoxin:NADPþ oxidoreductase with the
PBSs strongly suggests that a certain amount
of this enzyme is bound to the PBSs [19]. An-
other protein, NblA, first identified as required
for PBS degradation [20], also copurifies with
PBSs [21].
III. PIGMENT BIOSYNTHESIS
The pigments attached to the PBs are linear tetrapyr-
roles, called phycobilins. They are bound to the pro-
tein moiety at conserved positions by cysteinyl
thioether linkages through the vinyl substituent of
the pyrrole ring A. Occasionally, a second linkage is
established through the vinyl substituent of the pyr-
role ring D [2]. Phycobilin synthesis follows the same
pathway as Chl until the metal chelation step. As

© 2005 by Taylor & Francis Group, LLC

these steps are described in detail in another chapter
(see Chapter 3), they will be only summarized here.
Like for the production of Chl molecules, the phyco-
bilin biosynthetic pathway starts with the synthesis of
d-aminolevulinic acid molecules, which are formed
along the Beale pathway [22]. This pathway requires
the activity of three enzymes, namely tRNAGlu(UUC)
ligase, also termed glutamyl-tRNA synthetase [23],
a NADPH:glutamate tRNA dehydrogenase [24],
and a glutamate 1-semialdehyde aminotransferase
(reviewed in Chapter 3). The dehydrogenase catalyzes
the conversion of Glu-tRNAGlu to glutamate 1-semi-
aldehyde and the glutamate 1-semialdehyde amino-
transferase converts glutamate 1-semialdehyde into
d-aminolevulinic acid through transaminations. The
aminotransferase from Synechococcus sp. PCC 6301
has been purified, and its N-terminal amino acid
sequence show significant similarities with that from
barley [24]. Subsequent intermediates are uropor-
phyrinogen III, coproporphyrinogen III, and proto-
porphyrin (Proto) IX (Cyanidium caldarium, [25]).
The route by which Proto-IX is converted into linear
bilins was resolved in 1981 after administration of
[14C] heme to Cyanidium caldarium. The resultant
phycocyanobilin was radiolabeled [26]. The direct
proof that heme is a biosynthetic intermediate in
phycobilin synthesis implied the existence of the en-
zymes ferrochelatase, catalyzing iron insertion into
Proto-IX, and the NADPH:heme oxygenase, per-
forming heme oxidative degradation to biliverdin
IXa. Such enzymes have indeed been found in the
genomes of completely sequenced cyanobacteria
(http://www.kazusa.or.jp/cyano/). Using 18,18O2, it
was shown that a heme oxygenase opens the heme
molecules by incorporating two different oxygen mol-
ecules to yield biliverdin IXa [27,28]. The enzyme is
soluble [27]. Full activity requires two reductants:
ferredoxin and soluble vitamin E or ascorbate, with
the vitamin as the most efficient cofactor [29]. Heme
oxygenase is encoded by the gene ho1 [30]. Light
regulates the production and activity of ferrochela-
tase [31]. Biliverdin IXa is then transformed to 3Z-
isomers of phycocyanobilin [29], which, in turn, bind
to the apoprotein [27] via a thioether linkage to cystei-
nyl residues [32–34]. Phycoerythrobilin was shown to
be an intermediate in this pathway [35], but an alter-
native route has recently been described [36]. Syne-
chocystis PCC 6803 cells can accumulate only
pigmented PBS proteins [29]. Chromophore attach-
ment seems to stabilize the structure and enhance
subunit binding of the ab monomers [37]. How the
synthesis of pigments and apoproteins are coupled is
still under debate. Whether the pigmented proteins
and the nonpigmented ones assemble spontaneously
or require chaperones remains to be determined. One
© 2005 by Taylor & Francis Group, LLC
model for the assembly of PBSs, based on numerous
experimental observations obtained with mutants,
proposed that the main control would operate at the
level of the formation of the ab monomers [38]. In
agreement with this, it was found that for the synthe-
sis of PEC the release of the holo-a subunit from its
complex with the chromophore lyase would be medi-
ated by the formation of the holo-a–holo-b hetero-
dimer [17].
IV. GENOME ORGANIZATION
The number of components, as well as the number of
transcriptional units encoding the PBS components
varies between species. Table 23.1 lists the compon-
ents that can be found in PBSs together with the
corresponding gene names. Gene clustering also
widely differs: the 22 PBS-related genes of Anabaena
PCC 7120, as well as the 15 of Themosynechococcus
elongatus BP-1, are grouped into five clusters,
whereas nine clusters exist for the 15 genes of Syne-
chocystis PCC 6803 (Table 23.2). The genes that code
for the a and b subunits of a given PB are usually
adjacent and cotranscribed. For the core AP, apcA
(a) is located upstream of apcB (b), while for the rod
PBs (PC, PE, and PEC) the gene coding for b pre-
cedes the one coding for a. The genes for the linker
polypeptides are often adjacent and cotranscribed
with those encoding the PB with which they are spe-
cifically associated [4,6]. The genes coding for the two
subunits of the PB a-subunit phycobilin lyases, which
attach the chromophore to the a apoproteins, are
often adjacent to and part of the corresponding phy-
cobiliprotein operon.
Although the clustering and location of the genes
on the chromosome is highly variable, all of the
genes required for the building up of functional
PBSs are regulated tightly in a coordinated manner.
No free PBs or phycobilins are found in cyanobacter-
ial cells under standard conditions. Differences have
been reported in the level of stable transcripts corre-
sponding to the genes that constitute an operon. As
an example, apcEABC, apcABC, apcAB, and apcC
mRNAs have been found in Tolypothrix PCC 7601,
with the same 5’-end for the apcABC and apcAB
transcripts [39]. Whether they correspond to start
sites originating from internal promoters or to stable
processed products remains to be established. It is
worth noting that the relative ratio between the dif-
ferent mRNAs reflects the relative abundance of the
gene products within the PBS, the apcAB transcripts
being by far the most abundant. Gene families have
been found for a few genes but the specific roles
of each of the gene products is largely unknown:
TABLE 23.2
Physical Organization of the Genes Related to Phycobilisome Biosynthesis in Three Fully Sequenced
Cyanobacterial Geneomes. Gene Assignments were taken from Cyanobase (http://www.kazusa.or.jp/cyano/)
Cluster Gene Gene Product Gene Assignment

Anabaena/Nostoc sp. PCC 7120

7120 cluster 1 apcF b18.3 Allophycocyanin b-type subunit all2327
7120 cluster 2 apcE LCM terminal energy acceptor alr0020
apcA aAP Allophycocyanin a subunit alr0021
apcB bAP Allophycocyanin b subunit alr0022
apcC LC small core linker asr0023
7120 cluster 3 apcD aAPB Allophycocyanin B all3653
7120 cluster 4 apcA2 Allophycocyanin a-type subunit all0450
7120 cluster 5 pecB bPEC Phycoerythrocyanin beta chain alr0523
pecA aPEC Phycoerythrocyanin alpha chain alr0524
pecC LRPEC PEC-associated rod linker protein alr0525
pecE Phycobiliviolin lyase a subunit alr0526
pecF Phycobiliviolin lyase b subunit alr0527
cpcB bPC Phycocyanin beta chain alr0528
cpcA aPC Phycocyanin alpha chain alr0529
cpcC LRPC PC-associated rod linker protein alr0530
cpcD LRPC small rod linker polypeptide asr0531
cpcE Phycocyanobilin lyase a subunit alr0532
cpcF Phycocyanobilin lyase b subunit alr0533
cpcG1 LRC rod–core linker polypeptide alr0534
cpcG2 LRC rod–core linker polypeptide alr0535
cpcG3 LRC rod–core linker polypeptide alr0536
cpcG4 LRC rod–core linker polypeptide alr0537

Thermosynechococcus elongatus BP-1

BP-1 cluster 1 apcA aAP Allophycocyanin a subunit tll0957
apcB bAP Allophycocyanin b subunit tll0956
apcC LC small core linker tsl0955
BP-1 cluster 2 apcD aAPB Allophycocyanin B tll1551
BP-1 cluster 3 apcE LCM terminal energy acceptor tll2365
BP-1 cluster 4 apcF b18.3 Allophycocyanin b-type subunit tlr2034
BP-1 cluster 5 cpcB bPC phycocyanin beta chain tlr1957
cpcA aPC Phycocyanin alpha chain tlr1958
cpcC LRPC PC-associated rod linker protein tlr1959
cpcD LRPC small rod linker polypeptide tlr1960
cpcE Phycocyanobilin lyase a subunit tlr1961
cpcF Phycocyanobilin lyase b subunit tlr1962
cpcG1 LRC rod–core linker polypeptide tlr1963
cpcG2 LRC rod–core linker polypeptide tlr1964
cpcG4 LRC rod–core linker polypeptide tlr1965

Synechocystis sp. PCC 6803

6803 cluster 1 cpcB bPC Phycocyanin beta chain sll1577
cpcA aPC Phycocyanin alpha chain sll1578
cpcC2 LRPC PC-associated rod linker protein sll1579
cpcC1 LRPC PC-associated rod linker protein sll1580
cpcD LRPC small rod linker polypeptide ssl3093
6803 cluster 2 cpcG2 LRC rod–core linker polypeptide sll1471
6803 cluster 3 cpcG1 LRC rod–core linker polypeptide slr2051
6803 cluster 4 cpcE Phycocyanobilin lyase a subunit slr1878
6803 cluster 5 cpcF Phycocyanobilin lyase b subunit sll1051
6803 cluster 6 apcD aAPB Allophycocyanin B sll0928
6803 cluster 7 apcE LCM terminal energy acceptor slr0335
6803 cluster 8 apcF b18.3 Allophycocyanin b-type subunit slr1459
6803 cluster 9 apcA aAP Allophycocyanin a subunit slr2067
apcB bAP Allophycocyanin b subunit slr1986
apcC LC small core linker ssr3383

© 2005 by Taylor & Francis Group, LLC

cpcG1-2 in Synechocystis PCC 6803 code for slightly
different core — rod linkers (up to four have been
found in Anabaena PCC 7120; [40]); apcA2 code for a
second a-type AP subunit in Tolypothrix PCC 7601
and Anabaena PCC 7120, but no function has yet
been attributed to ApcA2 ([41]; http://www.kazusa.
or.jp/cyano/Anabaena/) and, nblA1-2 specify two
NblA polypeptides [42].
V. TRANSCRIPTIONAL REGULATIONS
INDUCED BY ENVIRONMENTAL
CHANGES: A COMPLEX INTRICATE
NETWORK
It is well established that the composition and the
number of PBSs per surface unit of thylakoidal mem-
brane vary in response to environmental changes such
as intensity and spectral quality of light and nutrient
availability (e.g., [6]). The effects of these two kinds of
stress will be discussed.
A. NUTRIENT AVAILABILITY
Nitrogen is a key element that accounts for approxi-
mately 10% of the dry weight of a cyanobacterial cell
[43]. Under standard conditions, cyanobacteria use
ammonium, nitrate, urea, or amino acids (in decreas-
ing order of preference) to satisfy their nitrogen re-
quirements, a number of strains also being able to
grow on molecular dinitrogen [44]. Whatever the ini-
tial source, ammonium is produced and assimilated
through the central glutamine synthetase/glutamate
synthase cycle, so-called GS-GOGAT pathway (Fig-
ure 23.1). Nitrogen starvation has pleiotropic effects
on cell metabolism: it triggers the expression of genes
involved in nitrate and nitrite uptake and assimila-
tion, and the degradation of the PBSs. Indeed, be-
cause PBSs may constitute nearly half of the soluble
proteins of a cyanobacterial cell, they represent an
important source of nitrogen (reviewed in Ref. [45]).
Degradation of PBSs leads to the depigmentation of
the cells, which turn from blue-green to yellow-green,
a phenomenon known as chlorosis [46,47]. Electro-
phoretic studies have revealed a sequential degrad-
ation from the distal end of the rods towards the
central core of the PBS [47], i.e., essentially the reverse
of the assembly process [4,48].
Mutants of Synechococcus sp. PCC 7942 that do
not bleach when grown under nitrogen starvation con-
ditions have been selected and have led to the identifi-
cation of the so-called nbl (nonbleaching) genes: nblA
encodes an ~7-kDa polypeptide, nblB the product of
which shares similarities with phycobilin lyases, nblR
and nblS code, respectively, for a response regulator
© 2005 by Taylor & Francis Group, LLC
and a histidine kinase, typical of bacterial two-com-
ponent systems [20,49–51]. In Synechococcus PCC
7942, the nblA gene is transcribed under nitrogen-
and sulfur-limiting growth conditions [20], whereas
in Synechocystis PCC 6803 the transcription of the
two tandem copies of nblA is only activated by nitro-
gen deficiency [42]. nblA genes are present in all PBS-
containing strains with the exception of the marine
strains (http://www.kazusa. or.jp/cyano and http://
www.jgi.doe.gov/JGI_microbial/html), may be be-
cause the latter live in a more stable environment
(Figure 23.1). Although an nblA gene is necessary for
PBS degradation, it may not be the triggering factor
since it was found to be expressed in Tolypothrix sp.
PCC 7601 cells grown under nitrogen-replete condi-
tions [21]. The precise mechanism by which NblA
proteins act in PBS degradation remains to be eluci-
dated. NblA may tag or provoke a conformational
change of the PBSs, which would then be degraded
by a protease induced by starvation conditions. On the
other hand, it has been shown that nblA mutants of
both Synechocystis PCC 6803 and Synechococcus PCC
7942 enter, under N-limiting conditions, a nondividing
dormant state which suggests pleiotropic effects of
NblA on cell physiology [52,53]. For Synechococcus
PCC 7942, the transcription of nblA is controlled by
NblR and NtcA, a global nitrogen regulator (see
below), under nitrogen starvation, but only NtcA
under conditions of sulfur deficiency [54].
The function of NblB still remains to be deter-
mined. Its similarities with the phycobilin lysases sug-
gest that it could take the chromophore off the PBSs,
thereby rendering these PBSs susceptible to proteoly-
sis. nblR codes for a response regulator typical of the
two-component systems, and NblS appears to be the
cognate histidine kinase that will form with NblR a
signal transduction pathway controlling general accli-
mation responses [51]. The global regulator NtcA [55]
is present in all cyanobacteria examined so far ([44],
http://www.kazusa.or.jp/cyano and JGI). It belongs
to the cAMP receptor protein (CRP) family of
transcriptional regulators [56]. It bears close to its
C-terminal end a helix–turn–helix motif for inter-
action with DNA, and acts as a dimer, each subunit
making contact with one half of a palindromic recog-
nition sequence GTA-N8-TAC [57]. NtcA binding
sites have been found in the promoter regions of
nblA genes, but the role of NtcA in controlling nblA
transcription has only been demonstrated to date in
Synechococcus PCC 7942 [42,54].
B. STRESS BY LIGHT
While sunlight provides the energy for photosyn-
thesis, high visible light intensity and UV light injure
 Fe
nbl B
PCB Biliverdin-IXalpha Heme Proto-IX ALA
Apoproteins Heme
NblR (PC-AP) oxygenase Fe-chelatase
NblB Mg
nblR PBS
Co-Proto-IX
Sn-Proto-IX Mg-chelatase
P NblS NblA Co
ho1
Excess light nblA Sn Fe-
Nitrogen starvation chelatase
Visible
light
PBS degradation chl H
pathway Chl
Standard nblS UVB or
conditions high-light
NtcA intensity
PAR
ntcA
glnB

Phosphatase P

PII PII
Nitrite/nitrate
Kinase 2-Oxoglutarate
uptake genes Low-affinity inorganic carbon-
rbcLS transport and concentration
mechanism gene (ccm genes)
Nitrate/nitrite 2-Oxoglutarate
Glutamine Low-affinity inorganic
assimilation system Krebs carbon-transport and
NO3 NO2 Cycle concentration mechanism
NH4 GS/GOGAT cycle Rubisco High-affinity inorganic carbon-
Succinyl CoA CO2 transport and concentration
Glutamate Calvin High-affinity inorganic mechanism gene (ccm genes)
Cycle carbon-transport and
concentration mechanism

FIGURE 23.1 Schematic representation of the links between metabolic and regulatory pathways for the control of PBS biosynthesis and degradation following nitrogen or
light stresses. Arrows represent controls either at a transcriptional or at a post-transcriptional level. It should be noted that the scheme has been built using data from several
species of cyanobacteria. All links have not yet been directly ascertained and it is known that there exist differences between cyanobacterial species that likely are related to the
ecological niches in which they are living.

© 2005 by Taylor & Francis Group, LLC

many organisms, and their responses to such stresses
vary with strains (for a review, see Ref. [6]). Gross-
man et al. [58] have recently reviewed the effect of the
light environment on PBS composition, in particular
during complementary chromatic adaptation, and we
will therefore not discuss this phenomenon here.
Changes in the spectral quality or intensity of visible
light trigger another cellular response known as the
‘‘state transition’’. This cellular defense mechanism is
rapidly initiated in order to regulate the transfer of
light energy between the two PSs. The state transition
model predicts that the ‘‘excess’’ energy absorbed by
PBSs associated with PSII is directed preferentially to
PSI; cells are then said to be in state 2. Three models
have been proposed: the ‘‘mobile PBS model’’ (move-
ment of the PBS between PSII and PSI), the ‘‘spill-
over’’ model (change in the rate of energy transfer
from PSII to PSI chlorophyll molecules), and the
‘‘detachment model’’ (detachment of PBSs from
PSII) (reviewed in Ref. [59]). Fluorescence recovery
experiments after photobleaching treatment have in-
dicated that PBSs could be more mobile than PSII
[60]. However, experimental evidences such as (i) state
transitions that occur in mutants devoid in PBS [61],
(ii) the absence of reversible phosphorylation–depho-
sphorylation process, which, in chloroplasts, is in-
volved in state transitions [62], and (iii) in vitro
experiments performed with isolated PSI and PSII
[63] make the ‘‘spillover’’ model the most likely. Mu-
tants of the apcD gene (Table 23.1) have been shown
to be impaired in state transition and appear to be
blocked in state 1 (Synechococcus sp. PCC 7002: [64];
Synechocystis PCC 6803: [65]). Insertional inactiva-
tion of the Synechocystis PCC 6803 ORFsll1926
(rpaC ¼ regulator of PBS association) also prevents
state transitions [66]. Rigidification of membranes,
occurring naturally under low-temperature stress or
provoked by engineering strains, was shown to influ-
ence state transitions [67]. State transitions are an
example of the physiological changes that occur in
photosynthetic organisms to cope with changes in the
light quality and intensity of UV-B and white light,
but little is known about the regulatory networks
controlling the response. It is worth mentioning that
recent data showed that the transfer of excitation
energy harvested by the PBSs directly to PSI has
been highly underestimated [68].
Global analyses of the transcriptional modifica-
tions triggered by high-intensity visible light or
UV-B irradiation, using the cDNA microarray tech-
nology, have been reported recently [69,70]. In
addition to the downregulation of PS I gene expres-
sion, there was a coordinated decrease of most of the
genes encoding structural subunits of PBSs, including
apcA, apcB, apcC, apcD, apcE, apcF, cpcB, cpcC,
© 2005 by Taylor & Francis Group, LLC
cpcD, and cpcG. The genes encoding key enzymes
of the biosynthetic pathway for tetrapyrroles,
i.e., hemA (NADPH:glutamate-tRNAGlu reductase),
hemF (coproporphyrinogen oxidase), and ho (heme
oxygenase) are also downregulated. In contrast, the
expression of the genes encoding PC-phycocyanobilin
lyase (cpcE, cpcF ) is not affected. Interestingly, the
expression of nblA is upregulated by a factor of 3 to 8
but whether this activation is directly triggered by the
UV-B irradiation remains to be elucidated. UV-B
downregulates genes involved in CO2 fixation, i.e.,
Rubisco (rbcL and rbcS genes) [70] (Figure 23.1). It
is interesting to note that in Anabaena PCC 7120 the
rbcL promoter presents a site at which NtcA can bind
[71,72]. UV-B also represses the constitutive low-
affinity inorganic carbon-transport and concentrating
mechanism proteins (ccm genes) (Figure 23.1). There-
fore, under UV-B irradiation, the cellular CO2 in-
come would decrease. Consequently, the cellular
concentration in 2-oxoglutarate would also be pro-
gressively reduced since the Krebs cycle will be less
productive as a result of the reduction in the Calvin
cycle activity. Because 2-oxoglutarate is at the heart
of the GS/GOGAT cycle, through which all cellular
nitrogen is incorporated (Figure 23.1), UV-B irradi-
ated cells would be rapidly depleted in nitrogen. As
described above (Section V.A), nitrogen deficiency
triggers the activation of the ntcA gene and PBS
degradation, as well as the activation of the synthesis
of the nitrate assimilation system. The latter would
however not occur if the cellular 2-oxoglutarate con-
centration is low because it requires the phosphoryl-
ated form of the PII (GlnB) protein, the formation of
which requires 2-oxoglutarate [73] (Figure 23.1).
The increase in the intensity of visible light from
25 to 200 mmol/m2/s produces responses similar
to those induced by an UV-B irradiation at 60 mE/
m2/s1 [70]. This suggests that the regulatory networks
controlling PBS biosynthesis and functioning under
these two conditions involve common intermediates.
Time-course studies using quantitative RT-PCR, as
well as analyses of the proteome by two-dimensional
gels will be necessary to elucidate the order of the
events that allow cells to appropriately modify their
metabolism and cope with the changes that occur in
their environment.
VI. REGULATORY LOGIC
As pointed out in the preceding sections, the synthesis
and degradation of PBSs is highly regulated and must
respond to multiple environmental influences. The
regulatory network controlling PBS synthesis and deg-
radation dynamically integrates these environmental
parameters, most important among which are light
intensity and quality, as well as availability of
carbon, nitrogen, and other essential nutriments.
In order to fully understand the functioning of this
regulatory network we would need to know all
(or at least most) of the regulatory components in-
volved, their interactions, as well as the kinetic con-
stants describing these interactions. Unfortunately, we
are still far from this goal and at present we have to
resort to a more intuitive understanding of the regula-
tory logic.
The analysis is complicated by the fact that the
PBS system combines genetic regulatory controls
(gene expression, protein stability, etc.) and meta-
bolic control (intracellular concentration of metabol-
ites that influence enzymatic reaction rates). This
latter type of control acts on a much faster time-
scale than the former and we consider metabolic
adaptation as essentially instantaneous in our dis-
cussion, which therefore focuses mainly on genetic
control.
A. CONTROL OF PBS SYNTHESIS AND DEGRADATION
The rate of synthesis of the PBSs is determined by the
metabolic state of the cell, as described in the previous
paragraph. The genetic control of PBS synthesis is
primarily exerted at the level of expression of the
apc and cpc genes. Although some of the transcrip-
tion start sites have been mapped, no in depth studies
of the promoter regions have been performed, and
little is known about transcriptional control of these
genes. Their expression is greatly diminished under
conditions of nitrogen starvation [74]. In Synechocys-
tis PCC 6803, the transcription of the photosynthetic
genes ( psa, psb, apc, and cpc), as well as of nblA, is at
least in part controlled by the two-component re-
sponse regulator RppA [75]. At present it is not
clear what physiological or environmental signal is
exactly detected by the putative sensor kinase RppB.
Induction of NblA expression promotes, directly
or indirectly, the degradation of PBS; NblA being a
protein that is necessary, but not sufficient, for the
degradation of PBS. The less well characterized pro-
tein NblB also participates in the degradation of PBS
together with at least one other protein, a protease,
which remains to be discovered. Analysis of the tran-
scriptional control mechanisms of the nblA gene
shows a direct influence of NtcA and NblR [54].
These multiple, often redundant or parallel sensory
inputs into the control of PBS synthesis and degrad-
ation, connect the PBS to all major physiological and
environmental parameters sensed by the cells. Figure
23.2 shows a summary of some of the known regula-
tory connections.
© 2005 by Taylor & Francis Group, LLC
B. THE KEY REGULATORY PROTEINS
At least three global regulators are intimately in-
volved in the regulatory network controlling PBS
expression: NtcA, NblR, and SigE. Even though
each one of these regulators acts on the PBS system,
they each have multiple other regulatory connections
to different control circuits in the cell. NtcA has been
described as the central regulator of nitrogen metab-
olism, and its homologs are found in many cyanobac-
teria [44]. The ntcA gene is transcribed from a single
or multiple promoters, depending on the cyanobac-
terial species, and its expression is repressed by NH4.
For the marine Synechococcus WH7803 this occurs at
the posttranscriptional level through a reduction in
the mRNA half-life [76]. Further control of NtcA
activity may be exerted through 2-oxoglutarate,
which modulates the affinity of NtcA to its DNA-
binding sites. The control circuits are rather complex;
the transcription of the ntcB gene, for example, is
activated by NtcA and both proteins activate simul-
taneously the expression of the nir operon, i.e., the
genes responsible for nitrate uptake and assimilation.
Furthermore, many other genes possessing NtcA
binding sites have been identified in different cyano-
bacteria. In Anabaena PCC 7120, NtcA is involved in
the control of heterocyst formation, may control the
global regulator HU [77], and binds to the promoter of
the rbcL gene (ribulose bisphosphate carboxylase),
thereby linking carbon and nitrogen metabolism. Fur-
thermore, NtcA activates the transcription of sigE in
Synechocystis PCC 6803. This sigma factor, also called
rpoD2-V, is important for survival under conditions of
nitrogen starvation but deletion of this gene affects the
transcription of many other genes unrelated to nitro-
gen metabolism (unpublished results). As all class II
sigma factors, SigE directs the transcription of a well-
defined class of genes and thereby changes profoundly
the transcriptional profile of the cell. Identification of
the members of this regulon is underway and prelim-
inary results show a connection between SigE and
the transcription of genes involved in photosynthesis
(unpublished results).
Another central building block of the regulatory
system is the response regulator NblR. The import-
ance of this regulator lies in the fact that the activity
of this protein, its phosphorylation state, is affected
by a number of different physiological conditions. An
nblR mutant rapidly dies during sulfur or nitrogen
starvation or after exposure to high light. NblR is
thus the target of kinases that detect various stresses
to the cell. The sensor kinase NblS may be the cog-
nate histidine kinase transferring the phosphate to
NblR, even though this hypothesis has not yet been
demonstrated experimentally [51]. This sensor kinase
 Environmental High light Stress
stress UV - light response
High
metabolite
availability
NblS X

HliA
NblR NblR~P Apc
Cpc

RppA ?
RppB

NtcA NblA PBS

NblB

GifA
SigE
GifB
?

GlnN GlnA C/N balance

PII PII~P

N sources Glutamine

Inhibition
PphA
Degradation

Activation

Transformation

FIGURE 23.2 Regulatory connections controlling the synthesis and degradation of PBSs. The same symbols are used for
activating of repressing interactions irrespective of the molecular mechanism (transcription, translation, activity, etc.).
Transformations of one molecule into another, e.g., phosphorylation, are denoted by a full arrowhead. Most of the
known regulatory interactions are indicated and some of the putative or missing interactions are denoted by a question
mark. Future studies will further complicate this already highly connected network.

appears to detect multiple stresses such as UV light
and nutrient deprivation, as well as the redox state of
the cell. The signals emanating from other sensor
kinases may also converge to NblR. Even though
the only well-established target of NblR is NblA,
indirect evidence shows that NblR controls many
other genes. For example, an NblA mutant grows in
high light, whereas an NblR mutant does not. This
shows that signal transduction through NblR does
not necessarily pass on to NblA. Most of the targets
of the global transcription regulator NblR remain to
be identified.
C. COMMON THEMES OF REGULATION
The regulatory networks controlling the expression of
the PBSs are highly interconnected and controls are
exerted at all levels: enzyme activity, transcription,

© 2005 by Taylor & Francis Group, LLC

mRNA, and protein stability. Much of the genetic
control converges to NblA. However, at present we
do not yet know the molecular basis of many of the
interactions that constitute this intricate regulatory
circuit. Some of the uncertainties are indicated in
Figure 23.2 by question marks. This lack of informa-
tion precludes a detailed analysis of the dynamical
properties of the regulatory network. However, cer-
tain themes of construction can already be seen in the
still sketchy and incomplete scheme of Figure 23.2.
A large number of the signal transduction path-
ways utilize two-component systems (histidine
kinase–response regulator). Since a sensor kinase
never has an absolute specificity for only one response
regulator there is necessarily crosstalk between the
different systems. The path of signal transduction is
therefore never strictly linear; the response regulators
rather integrate environmental and physiological sig-
nals originating from very different sources. Further
integration is achieved by multiple controls of key
regulators, such as NblA or the PBS genes and pro-
teins themselves.
The response to a particular stress or physio-
logical state is not channeled to the key regulator
only via a single signal transduction pathway. On
the contrary, the network architecture ensures that
one particular signal is distributed to numerous
subsystems of the organism. For example, the car-
bon–nitrogen balance of the cell is probably detected
via the intracellular concentration of 2-oxoglutarate.
This ‘‘signal’’ is perceived not only by NtcA, which by
itself controls a large number of diverse target genes
[44], but also by PII (GlnB). One of the NtcA targets
is the sigma factor SigE (sll1689). The specific pro-
moter elements recognized by this sigma factor have
not yet been characterized, but being the subunit of
the RNA polymerase that confers specificity for gene
transcription, induction of this gene will certainly
profoundly affect the global transcriptional program
of the cell.
A third striking feature of the phycobilisome regu-
latory network is redundancy: the same signal is often
perceived by and/or acting on more than one trans-
duction pathway. For example, exposure to high light
results in the degradation of the PBS via the NblR–
NblA pathway as well as by an NblR-dependent but
NblA-independent route [49]. The upregulation of
nitrogen assimilation genes passes not only through
the activation of SigE and GlnN, but also through the
parallel pathway that relieves the inhibitory influences
of NtcA on GifAB, and in turn that of GifAB on
GlnA.
The high connectivity within this regulation net-
work, and our limited knowledge of the interactions
precludes precise model building of the dynamics for
© 2005 by Taylor & Francis Group, LLC
this system. Much of what we know is based on the
investigation of individual interactions that are
mostly organized in a linear manner. However, the
global behavior of the network, the stable states, and
the transitions between these states, must emerge
from intertwined positive and negative feedback
loops. At present we can apprehend the response of
the system in very specific conditions, but a true
understanding of the dynamics has to await the dis-
covery of at least some of the missing connections.
The recent development of DNA microarrays and
quantitative RT-PCR allow us to perform the global
analyses required for a more comprehensive under-
standing of the regulatory networks. In addition, we
expect that further levels of control, e.g., at transla-
tion, mRNA stability, etc., will emerge as this system
is further investigated.
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