concanamycin-a and glycolic-acid

The microbial macrolides bafilomycin A1, B, and concanamycin A from Streptomyces spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon "glycolate units" of each of the macrolide structures was addressed by feeding experiments with stereospecifically 13C-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C2-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.

Topics: Carbon Isotopes; Carboxylic Acids; Citric Acid Cycle; Glycerol; Glycerol Kinase; Glycolates; Macrolides; Metabolic Networks and Pathways; Molecular Structure; Streptomyces