118 TIBS- May 1979

E. co/i Acknowledgements Ames, B. N. and Neilands, J. B. (1972) J.

Bart. 111, 731-738
K-12
Research on siderophores and microbial ,, Wayne, R. ar,d Neiiands, J. B. (1974) MlCR
iron metabolism in the author’s laboratory 3, 16Sth National Meeting, Am. Chcm. SW.,
83K - - has been supported by NIH grants Atlantic City, Sept. 9-13
AM17146 and AI04156. 12 Wayne, R. and Neilands, J. B. (1975) J.
81K - - Butt. 121, 497- 503
13 Hactke, K. and Braun, V. (1975) FEBS
References Lett. 49, 301-30s
78K ___ ___
1 Warburg, 0. (1949) Heavy Metal Prosthetic 14 Luckey, M., Wayne, R. and Neilands, J. B.
Groups, Oxford Press (1975) Biochem. Biophys. Res. Commun.
2 Braun, V. and Hantke, K. (1977) in Microbial 64, 687-693
74K - - Interactions, Receptors and Recognition, Ser. 15 Luckey, M. and Neilands, J. B. (1976) J.
B, Vol. 3 (Reissig, J. I,., ed.), Chapman and Burt. 127, iO36- 1037
Hall, London, pp. lo%137 16 Postle, K. and Reznikoff, W. (1978) Abstr.
3 Neilands, J. B. (1977) in Bioinorganic Annual Meeting. Am. Sot. Microbial., Las
Fig. 4. Schematic illustration of SDS-polyacryl-
Chemistry II (Raymond, K. N.,, ed.), Am. Vegas, Nev., May 14-19, p. 113
amide gel electrophoretic patterns of high mole-
Chrm. Sot., Washington, pp. 3-32 17 Wookey, P. and Rosenberg, H. (1978) J.
cular weight ou!er membrane proteins from
Weidel, W., Koch, G. and Bobosch, K. Bac,t. 133, 661-666
Escherichia coli strains K-12 and B after growth
(1954) 2. Naturforsch. 96, 573-579 18 Wayne, R., Frick, K. and Neilands, J. B.
in low and high iron media (see text)
Fredericq, P. (1956) C. R. Sac. Biol. (Paris) (1976) J. Bact. 126, 7712
150, 1514-1517 19 Negrin, R. S. and Neilands, J. B. (1978) J.
of ferric enterobactin transport, since the DiMasi, D. R., White, J. C., Schnaitman, Biol. Chem. 253, 2339-2342
reaction has not been demonstrated in C. A. and Bradbeer, C. (1973) J. Biol. Chem. 20 Guterman, S. (1973) J. Bact. 114, !217-1224
vesicles. Likewise, it is not known if the 115, 506513 21 Uemura, J. and Mizushima, S. (1975)
receptor shows optical specificity for the 7 Neilands, J. B. (1976) in Development of Iron Biochim. Biophys. Acta 413, 163-l 76
Chelators for Clinical Use (Anderson, W. F. 22 McIntosh, M. A. and Earhart, C. F. (1976)
lambda or delta coordination isomer.
and Hiller, M. C., eds), Pub. No. NIH 76- Biochem. Biophys. Res. Commun. 70. 3 15-322
Ferric enterobactin binds one atom of 994, National Institutes of Health, Washing- 23 Hollifield, W. C. and Neilands, J. B. (1978)
Ca2+ with strong affinity in non-aqueous ton, pp. 5-44 Biochemistry 17. 1922-l 928
media, but the biological significance of 8 Garibaldi, J. A. and Neilands, J. B. (1956) 24 Hollifield, W. C., Fiss, E. H. and Neilands,
this is uncertain at the present time [25]. Nature 177, 526-527 J. B. (1978) Biochem. Biophys. Res. Common.
9 Decad, G. M. and Nikaido, H. (1976) J. (in press)
Future research Bact. 128, 325-336 25 Hider, R. C. and Neilands, J. B. (1978) (in
10 Luckey, M., Pollack, J. R., Wayne, R., preparation)
Obviously, the siderophore receptors
must be isolated, chemically charac-
terized and reconstituted into a function-
ing system in order to cast light upon the
molecular mechanics of the transport
50 Years Ago
process. Additionally, the relation of the
components seen on gels to the entire
receptor-transport complex
explored. Equally interesting
should
is the regu-
be Discovery of vitamin K
lation of the high affinity iron transport In 1929 Henrik Dam, a faculty member MacFarlane and his co-workers in Canada
system. Apart from these problems in of the Biochemical Institute of the Univer- and by Holst and Halbrook at the Univer-
basic research, opportunities exist for the sity of Copenhagen, was admitted for sity of California. By 1935 Dam and his
adaptation of concepts learned with doctoral study to the Biochemical Insti- co-workers had shown that none of the
microbes to diverse fields of biomedical tute of the University of Freiburg under established nutrients, including vitamins
science. Siderophores show promise for the direction of Professor Rudolph A, D, E and ascorbic acid could prevent
deferration of patients suffering from Schonheimer. Investigating cholesterol the disease and that the hemorrhage
transfusion-induced siderosis [7] and for biosynthesis in chicks, he undertook was due to a defect in the coagulation
chelation therapy in actinide intoxication. some preliminary balance studies using of the blood associated with a lack of
Siderophore receptors may prove to be a fat-free diets in Copenhagen in 1929. prothrombin. They concluded that the
vehicle for smuggling semi-synthetic anti- During the conduct of these studies he cause was the absence of a new fat-
biotics into the microbial cell. The capacity observed- an unexpected hemorrhagic soluble dietary factor which they named
to synthesize components of the high disease affecting muscle, gut and subcutan- vitamin K (for Koagulation). The new
affinity iron transport system may be a eous tissues occurring after 2-3 weeks vitamin was found to be distributed in
prime determinant of virulence in micro- on this diet which was not responsive liver, hemp seeds and green leafy
bial infections of animals and plants. to lemon juice or dietary cholesterol [l]. vegetables.
Siderophore activity can easily be demon- He spent the next few years in Freiburg In 1965, on the occasion of the retire-
strated in soil, but the role of these completing his derctoral work on choles- ment of Edward A. Doisy of St. Louis
ligands in dissolution of minerals has not terol biosynthesis. On his return to University, with whom he shared the
been examined carefully, nor has the Copenhagen in 1933, however, he again Nobel prize in physiology and medicine
nutritional and health-related significance turned to the investigation of the unknown in 1943, Professor Dam reminisced about
of their presence in the gastrointestinal dietary factor required for normal hemo- his early work on vitamin K. He said his
tract, in sakt and in mold-ripened cheese stasis. In the meantime this hemorrhagic discovery was the result of pure seren-
been ascertained. disease had been reported in chicks by dipity, which some people have come to

@ El~vier/North-Holland Biomedical Press 1979