Biosynthesis of phenazine antibiotics in Streptomyces antibioticus: Stereochemistry of methyl transfer from carbon-2 of acetate

Stable isotope labeling experiments have shown that thr biosynthesis of the monomeric phenazines, the saphenyl esters, and their dimerization products , the esmeraldins, in Strepromyces antibioticus Tu 2706 proceeds from phena zine-1,6-dicarboxylic acid by chain extension with C-2 of acetate to 6-acet ylphenazine-1-carboxylic acid, which is reduced to saphenic acid. The latte r is incorporated into both halves of the esmeraldins, albeit differentiall y. By feeding of chiral acerate, degradation of the resulting saphenyl este rs and esmeraldins, and configurational analysis of the acetic acid formed, the chain extension process was found to proceed with overall inversion of configuration at the methyl group. This suggests that the decarboxylation of a hypothetical intermediate beta-keto acid proceeds in an inversion mode . This result is discussed with reference to analogous C-methylations of po lyketide backbones by addition of C-2 of acetate,