Biosynthesis of chloramphenicol

Abstract

The current knowledge concerning the biosynthesis of chloramphenicol is discussed. Cultures of Streptomyces sp. 3022a fed ¹⁴C‐shikimie acid incorporated the label to the same extent into phenylalanine, tyrosine, and chloramphenicol. Of possible precursors of the phenylpropanoid nucleus of this antibiotic only p‐aminophenylalanine and DL‐threo‐p‐amino phenylserine specifically labeled chloramphenicol. On the basis of these results a pathway for the biosynthesis of chloramphenicol is presented. The lack of specific incorporation of ¹⁵N‐nitrogen from a competitive feeding experiment in which both ^l5N‐nitrate and ¹⁴N‐DL‐serine were fed to growing cultures suggests that both the amido‐ and the nitro‐nitrogen atom present in this antibiotic are derived from a common pool. Studies on the enzyme, DAHP synthetase, show that in streptomyces sp. 3022a it is not subject to feed back inhibition by either phenylalanine, tyrosine, or chloramphenicol.