THE BIOSYNTHESIS OF THE STREPTOMYCES ANTIBIOTIC BICYCLOMYCIN

Abstract Bicyclomycin 5 is biosynthesized in Streptomyces sapporonensis from L-leucine 2 and L-isoleucine 1 by way of the naturally occurring diketopiperazine 3 and dihydrobicyclomycin 4 . The mode of incorporation of (2 S ,4 R )-[5,5,5- 2 H 3 ]leucine into 5 (and 4 ) shows that the entry of the hydroxy group at C-2′ occurs with unusual inversion of configuration. The results of inhibition studies permit a useful working hypothesis to be advanced for bicyclomycin biosynthesis.