DIRECTED BIOSYNTHESIS OF NEW SAFRAMYCIN DERIVATIVES WITH RESTING CELLS OF STREPTOMYCES-LAVENDULAE

Saframycin A is an antitumor antibiotic produced by S. lavendulae 314 which falls into the category of the N-heterocyclic quinone group. Biosynthetically the quinone ring is derived from 2 tyrosine molecules which condense to generate the basic ring system of saframycin A. A side chain is derived from 2 amino acids, i.e., glycine and alanine. Supplementation by various amino acid analogs of the side chain produced 3 new saframycin derivatives with a replaced side chain. These 3 saframycins, designated Yd-1, Yd-2 and Yd-3, contained 2-amino-n-butyric acid, glycine and alanine residues, respectively, in place of the normal N-terminal pyruvic acid in the side chain of saframycin A. Feeding experiments with 13C-labeled dipeptide indicated that the amino acids are probably incorporated in the side chain as a dipeptide unit. Saframycin A is produced from saframycin Y3 by an enzymatic deamination reaction. Saframycin biosynthesis in S. lavendulae is discussed.