Chloramphenicol biosynthesis, media

Mach, Reich and Tatum were able to demonstrate an inhibition of the biosynthesis of protein in cells of B. brevis by chloramphenicol and puromycin without affecting the synthesis of tyrocidine . Several analogues of amino acids were found, which inhibited the biosynthesis of tyrocidine without affecting that of protein and vice versa. In contrast to protein synthesis, the production of tyrocidine did not depend on the continuous synthesis of RNA. Furthermore, environmental factors were able to control the relative amounts of the different tyrocidines synthesized by genetically homogeneous cultures . Addition of phenylalanine to the culture medium resulted in the almost exclusive synthesis of tyrocidine A, whereas the unsupplemented culture produced tyrocidine A, B and C. In the presence of tryptophan, a new form of tyrocidine, called tyrocidine D, containing three tryptophan in place of three phenylalanine residues, was produced. This lack of absolute requirement for specific amino acids in the formation of a peptide bond is in contrast to the strict specificity of sequential incorporation of amino acids... 

Chloramphenicol has the common Ce-Cs skeleton which appears in amino acids such as phenylalanine and its C3 fragment is also structurally related to serine, but it contains a nitro group and dichloroacetyl group which are unusual in natural products. The condensation of />-nitrophenylserinol and dichloroacetic acid appears to have been excluded as a step in the biosynthesis of this antibiotic . However, dechloro analogues of chloramphenicol are produced by a Streptomyces sp. in a culture medium to which no chloride ion has been added. These analogues include compounds in which the dichloroacetyl group of XXVII is replaced by acetyl, propionyl, butyryl, and pentanoyl or hexanoyl . 

Table i. Chemically defined medium for the biosynthesis of chloramphenicol... 

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