BIOSYNTHESIS OF THE MANUMYCIN GROUP ANTIBIOTICS

The biosynthesis of the manumycin group antibiotics manumycin (1) and asukamycin (2) was studied in Streptomyces parvulus Tü 64 and Streptomyces nodosus ssp. asukaensis ATCC 29757 by using radioactive and stable isotope tracer techniques and high-field NMR spectroscopy. The results have demonstrated that the central, multifunctional mC7N unit typical of this group of antibiotics, which serves as the starter unit for a short polyketide chain, is biosynthesized from a C4 Krebs cycle and a C3 trióse phosphate pool intermediate by a new pathway, distinct from the shikimate, polyketide, or pentose phosphate routes leading to other mC7N units in nature. The C5 unit in both 1 and 2 arises by a novel intramolecular cyclization of 5-aminolevulinic acid, and a cyclohexane ring and the adjacent carbon in 2 arise from the seven carbon atoms of shikimic acid. The side chains of both antibiotics represent typical polyketide-derived moieties, differing with respect to their combinations of starter and elongation units. Results of isotopically labeled precursor feedings and precursor-directed biosynthesis experiments, in combination, allow predictions to be made about the biosynthetic assembly of the manumycin group antibiotics. © 1990, American Chemical Society. All rights reserved.