Biosynthesis of the macrolide antibiotic chlorothricin.
Feeding experiments with 13C-labeled precursors followed by 13C NMR analysis of the antibiotic and its aglycon have established a polyketide mode of biosynthesis for chlorothricin, a metabolite of Streptomyces antibioticus. The acyl moiety is a substituted 6-methylsalicylic acid derived from four acetate units and a methyl group of methionine. The aglycon is comprised of ten acetate and two propionate units, leaving three carbon atoms, C-22, -23, and -24, unaccounted for. The two 2-deoxy-D-rhamnose moieties are derived from glucose with retention of the hydrogens at C-1, C-2, and C-6 and loss of H-3 and H-5. The hydrogen at C-4 of glucose is transferred intramolecularly to C-6 of the hexose, replacing the hydroxyl group at C-6 in an inversion mode, a result which implicates the thymidine 5'-diphosphate-glucose oxidoreductase reaction in this transformation.
D000085:Acetates / Q000378:metabolism; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism; D006027:Glycosides / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D008715:Methionine / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D013302:Streptomyces / Q000378:metabolism*; D013303:Streptomyces antibioticus / Q000378:metabolism*
D000085:Acetates; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D006027:Glycosides; D011422:Propionates; D008715:Methionine; C000451:chlorothricin; D005947:Glucose