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

The biosynthesis of the antibiotic reductiomycin (1) in Streptomyces xanthochromogenus was investigated by feeding experiments with radioactive and stable isotope-labeled precursors. NMR and mass spectroscopic analyses of the labeled 1 samples revealed that the acetoxy group comes from acetate, the 2-amino-3-hydroxycyclopent-2-enone moiety arises by a novel intramolecular cyclization of 5-aminolevulinic acid (ALA), and the dihydrofuranylacrylic moiety is formed by aromatic ring cleavage 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 efficiently, 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 dioxygenase mechanism for the ring cleavage reaction and pyridoxal phosphate catalysis for the ALA cyclization.