Biosynthetic origin of the methoxyl extender unit in bafilomycin and concanamycin using stereospecifically labeled precursors.
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.
Schuhmann
Tim
T
Institut für Organische und Biomolekulare Chemie, Georg-August Universität Göttingen, Tammannstr. 2, Göttingen, Germany.
Vollmar
Daniel
D
Grond
Stephanie
S
D002247:Carbon Isotopes / Q000378:metabolism; D002264:Carboxylic Acids; D002952:Citric Acid Cycle; D005990:Glycerol / Q000378:metabolism; D005991:Glycerol Kinase / Q000378:metabolism; D006016:Glycolates / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D015394:Molecular Structure; D013302:Streptomyces / Q000378:metabolism*
D002247:Carbon Isotopes; D002264:Carboxylic Acids; D006016:Glycolates; D018942:Macrolides; C031149:glycolic acid; C036978:concanamycin A; C040929:bafilomycin A1; C052501:bafilomycin B1; D005991:Glycerol Kinase; D005990:Glycerol