STEREOCHEMISTRY OF C-3 DEOXYGENATION OF SUGAR NUCLEOSIDES - FORMATION OF PENTOPYRANINE-C FROM [3-H-2]-D-GLUCOSE BY STREPTOMYCES-GRISEOCHROMOGENES

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 S. 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-H-2]-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'-H-2]glucuronic acid, an 85:15 mixture of [3'-2H(axial)]- and [3'-H-2equatorial]PPNC, and a small amount of a 46:54 mixture of [3'-H-2axial]- and [3'-H-2equatorial]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.