BIOSYNTHESIS OF THE PHENYLPROPANOID MOIETY OF CHLORAMPHENICOL

Abstract

Cultures of Streptomyces sp. 3022a were grown in the presence of C¹⁴-labelled substrates and incorporation of radioactivity into chloramphenicol measured. D-Glucose, labelled in carbons 1 or 2 or uniformly, was an efficient precursor of the p-nitrophenylserinol moiety and of the phenylpropanoid amino acids of the mycelium. The distribution of label in the ring and side-chain carbon atoms of p-nitrophenylserinol and cellular phenylalanine from experiments in which glucose-1-C¹⁴, glucose-2-C¹⁴, and glycine-2-C¹⁴ were fed provided evidence that the two phenylpropanoid systems had a common biosynthetic origin. The results were also consistent with their formation via the shikimic acid – prephenic acid route. Uniformly C¹⁴-labelled shikimic acid, though poorly utilized by this organism, was incorporated selectively into both the aromatic portion of chloramphenicol and the aromatic amino acids in the mycelium. L-Phenylalanine-U-C¹⁴, L-phenylalanine-carboxyl-C¹⁴, L-tyrosine-carboxyl-C¹⁴, DL-p-hydroxyphenylserine-2-C¹⁴, and acetate-2-C¹⁴ were poor precursors of the p-nitrophenylserinol moiety. Since phenylalanine and tyrosine were incorporated into the mycelium the biosynthetic route to the phenylpropanoid portion of chloramphenicol evidently does not pass through either of these amino acids but branches at an earlier step.