Pfizer Handbook of Microbial Metabolites 686 



A more recent publication indicates that nine acetate 

 units are incorporated into the rutilanlinone molecule, 

 but that the three starred atoms are from propionate. ^°^ 

 Methionine would not, then, be involved in the side-chain 

 synthesis. 



Two investigations have been made on the chlorina- 

 tion mechanism of Streptomyces aureofaciens in the pro- 

 duction of aureomycin.^"^ "^ The authors of the first 

 reference concluded that incorporation of the chlorine 

 atom does not take place on the finished tetracycline 

 molecule, but at an earlier stage of biosynthesis. Wang's 

 results lead to the same conclusion. 



The influence of specific enzyme poisons on the produc- 

 tion of oxy tetracycline has been studied. ^•'^ Iron-contain- 

 ing oxidases and flavine oxidases participated in the 

 biosynthesis of oxy tetracycline. Phenoloxidase inhibi- 

 tors, on the other hand, stimulated production. 



There is httle agreement on the mode of action of the 

 tetracycline antibiotics, and it may be that they act in a 

 variety of ways. Inhibition of RNA and DNA synthesis 

 and inhibition of enzymic conversion of uracil to thy- 

 mine,^°^ binding by chelation of metal ions required by 

 coenzymes^-"' and blocking of unspecified biosynthetic 

 pathways^°^ have been mentioned. 



A discussion of the mechanisms of action of antibiotics 

 in general has been published. ^^"^ 



103 w. D. Ollis, I. O. Sutherland, R. C. Codner, J. J. Gordon and 

 G. A. Miller, Proc. Chem. Soc, 347 (1960). 



i°* J. Kollar and M. Jaral, Symposium on Antibiotics, Prague, 1959. 



105 E. Lin Wang, J. Antibiotics (Japan) 12A 31, 41, 50 (1959). 



loo V. Sevcik, V. Musilek and I. Komersova, Symposium on Anti- 

 biotics, Prague, 1959. 



10' T. Balakrishna Rao, D. V. Temhane, D. V. Rege and A. Sreeni- 

 vasan, "Antibiotics," Council of Scientific and Industrial Research, 

 New Delhi, 1958, p. 212. 



108 E. U. Weinberg, Bacterial. Revs. 21 46 (1957). 



10^ J. F. Snell, Florence Z. Thanassi and Dorothy Ann Sypowicz, 

 Antibiotics and Chemotherapy 8 57 (1958). 



110 S. G. Bradley and L. A. Jones, Annals N. Y. Acad. Sci. 89 123 

 (1960). 



