Studies of precursor-directed biosynthesis with Streptomyces sp. Part 1. Isolation of manumycin analogues by feeding of aminobenzoic acids as C7N starter units

Abstract

Feeding experiments involving variants of the antibiotic manumycin (1) are described. Instead of the (unidentified) natural C₇N unit, isomeric aminobenzoic acids were used as alternative biosynthetic starting units. These were fed to Streptomyces parvulus, and manumycin-like metabolites were produced. Use of 3-aminobenzoic acid suppressed the biosynthesis of (1) and resulted in the synthesis of the manumycin analogue 64-mABA (2), a new metabolite, the structure of which was determined. 4Aminobenzoic acid induced the production of 64-pABA (4), a metabolite without the chiral C₁₃ side chain of (1); 2-aminobenzoic acid was not incorporated. The implications of these results for the biosynthesis of the natural C₇N starter unit, for the specificity of the involved enzymes, and for the possibility of using natural product variation to produce structurally varied antibiotics are discussed.