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Antimicrob Agents Chemother. 1977 June; 11(6): 1056-1063
Copyright © 1977 American Society for Microbiology. All Rights Reserved.

Novel Actinomycins Formed by Biosynthetic Incorporation of cis- and trans-4-Methylproline

^* Department of Microbiology, Georgetown University, Schools of Medicine and Dentistry, Washington, D.C. 20007
¹ Research Foundation of the Washington Hospital Center, Washington, D.C. 20010

ABSTRACT

Streptomyces parvulus (Streptomyces parvullus) normally produces actinomycin D; in the presence of cis-4-methylproline, this species synthesizes two additional actinomycins, designated K_1c and K_2c, in which one and two proline sites, respectively, are occupied by cis-4-methylproline. Analogously, actinomycins K_1t and K_2t are formed in the presence of trans-4-methylproline. Both mixtures were separated chromatographically, and the four novel actinomycins were obtained in crystalline form. Their biological activities were compared with that of actinomycin D in respect to inhibition of ribonucleic acid, deoxyribonucleic acid, and protein synthesis and antimicrobial potency. In all cases examined, the order of activity D > K_1t > K_1c > K_2t > K_2c was observed, and the same sequence prevailed in a spectroscopic measure of their binding to deoxyribonucleic acid. In addition, proton nuclear magnetic resonance studies revealed that the replacement of proline by cis-4-methylproline alters the conformation of the antibiotic molecule.