H. Cho et al., STUDIES ON THE BIOSYNTHESIS OF THE ANTIBIOTIC REDUCTIOMYCIN IN STREPTOMYCES-XANTHOCHROMOGENUS, Journal of the American Chemical Society, 115(26), 1993, pp. 12296-12304
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.