STUDIES ON THE BIOSYNTHESIS OF THE ANTIBIOTIC REDUCTIOMYCIN IN STREPTOMYCES-XANTHOCHROMOGENUS

The biosynthesis of the antibiotic reductiomycin (1) in Streptomyces x anthochromogenus was investigated by feeding experiments with radioact ive and stable isotope-labeled precursors. NMR and mass spectroscopic analyses of the labeled 1 samples revealed that the acetoxy group come s from acetate, the 2-amino-3-hydroxycyclopent-2-enone moiety arises b y a novel intramolecular cyclization of 5-aminolevulinic acid (ALA), a nd the dihydrofuranylacrylic moiety is formed by aromatic ring cleavag e of a symmetrical product of the shikimate pathway. Both 4-hydroxy-[7 -C-13]benzoic acid and 4-hydroxy-[7-C-13]benzaldehyde label 1 very eff iciently, and deuterium from various positions in these precursors is incorporated into the predicted positions in the dihydrofuranylacrylic acid moiety of 1. The results are interpreted in terms of a dioxygena se mechanism for the ring cleavage reaction and pyridoxal phosphate ca talysis for the ALA cyclization.