Pfizer Handbook of Microbial Metabolites 274 



The production by Streptomyces rimosus of oxytetracy- 

 cline-X\ a modification of Terramycin in which there is an 

 acetyl group instead of a carboxamide group at position 2, sup- 

 ports the acetate theory since terramycin-X is more directly in 

 the line of descent from a polyketomethylene chain (ten head 

 to tail condensed acetate units) than is Terramycin itself. 



The dehydro derivatives which have been isolated- also may 

 be considered as precursors of the other tetracyclines since the 

 additional double bond may be the (as yet unreduced) result of 

 an aldol type of condensative ring closure with elimination of a 

 water molecule. 



More experimental work has been reported on the biosyn- 

 thetic origin of oxytetracycline than on that of related sub- 

 stances. Addition of C^Hj-methionine and 2-C^*-acetic acid to 

 oxytetracycline-producing fermentations yields radioactive oxy- 

 tetracycline (Terramycin). Quantitative degradation and 

 counting studies show that methionine furnishes the C,5-methyl 

 and the N-methyl groups. The radioactivity of the degradation 

 fragments from the molecule which had incorporated 2-C'^- 

 acetic acid indicated that most of the molecule is in quantitative 

 agreement with the theoretical requirements for acetate deriva- 

 tion.^' * 



Results are entirely consistent with formation of the ring 

 skeleton at least from C- to C^o by head to tail linkage of acetate 

 units. Glutamic acid has been considered as a possible precur- 

 sor of part of the A-ring (carboxamide side-chain, carbon atoms 

 2, 3, 4, 4a and the 4-amino nitrogen) and 2-C^ '-labeled glutamic 

 acid yielded a labeled oxytetracycline.-^ Later evidence'' indi- 

 cates that acetate also is capable of furnishing these carbon 

 atoms although the level of activity in the A-ring seems to be 

 somewhat lower than the theoretical, particularly in Terramycin 

 isolated from older fermentations. The degradation fragments 



^ F. A. Hochstein, M. Schach von Wittenau, Fred W. Tanner, Jr. 

 and K. Murai, /. Am. Chem. Soc. 82 (1960). (In press) 



- J. R. D. McCormick, Philip A. Miller, John A. Growich, Newell O. 

 Sjolander and Albert P. Doerschuk, ibid. 80 5572 (1958). 



3 A. J. Birch, J. F. Snell and P. L. Thompson, ibid. 82 2402 (1960). 



4 A. J. Birch and P. L. Thompson, ibid. 82 (1960). (In press) 

 ^ J. F. Snell, R. L. Wagner, Jr. and F. A. Hochstein, Internal. 



Conf. on Peaceful Uses of Atomic Energy, 431 (1955); J. F. Snell, 

 Symposium on Uses of Isotopes, Uniontown, Pa., 1957. 



'A. J. Birch and P. L. Thompson, ]. Am. Chem. Soc. 82 (1960). 

 (In press) 



