Stereochemistry of C-3 deoxygenation of sugar nucleosides: Formation of pentopyranine C from [3-2H]-D-glucose by Streptomyces griseochromogenes

Article abstract of DOI:10.1021/ja00052a014

Cytosylglucuronic acid (CGA) has previously been shown to be the first intermediate in the biosynthesis of the antibiotic blasticidin S (BS), produced by Streptomyces griseochromogenes. Addition of aminooxyacetic acid (AOAA), an inhibitor of pyridoxal phosphate/pyridoxamine phosphate-dependent transaminases, to 5. griseochromogenes fermentations led to substantial accumulations of CGA and pentopyranine C (PPNC, a shunt metabolite which has undergone decarboxylation at C-5′, deoxygenation at C-3′, and epimerization at C-4′) and to substantial reductions in the production of BS and N-demethylBS. In contrast, inhibitors of glutamine-dependent amidotransferases had little effect. [3-²H]-D-Glucose was fed to a fermentation of S. griseochromogenes containing arginine hydroxamate, an inhibitor of arginine biosynthesis, and a large quantity of cytosine-currently the best conditions for maximum production of CGA and PPNC. This yielded cytosyl[3′-²H]glucuronic acid, an 85:15 mixture of [3′-2H_axial]- and [3′-²H_equatorial]PPNC, and a small amount of a 46:54 mixture of [3′-²H_axial]- and [3′-²H_equatorial]pentopyranone (the immediate precursor to PPNC). The relationship of this C-3 sugar deoxygenation to blasticidin S biosynthesis and to the pyridoxamine phosphate-dependent CDP-4-keto-6-deoxy-D-glucose-3-dehydrase reaction which is central to cell-wall lipopolysaccharide biosynthesis of Gram-negative bacteria is discussed.