Limiting reactions in activation of acyl units in biosynthesis of macrolide antibiotics.
Formation of propionyl phosphate in Streptomyces erythreus synthesizing a polypropionate erythronolide ring of erythromycin was found to be catalyzed by a specific propionate kinase. The isolated and 100-fold purified kinase was devoid of activity towards acetate and other monocarboxylic acids. The selection for higher antibiotic-synthesizing ability was associated with higher kinase activity and lower K(m) values towards propionate. This relation did not apply to the mutants of S. noursei var. polifungini producing polyene tetraene antibiotics of the nystatin type, composed of acetate and propionate units. Instead, the antibiotic-synthesizing ability was correlated with the activity of acetyl- and propionyl-coenzyme A carboxylase, responsible for the formation of malonyl- and methyl-malonyl-coenzyme A intermediates in the polymerization process.
D000215:Acylation; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D003065:Coenzyme A / Q000378:metabolism; D003470:Culture Media; D004917:Erythromycin / Q000096:biosynthesis; D010770:Phosphotransferases / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003470:Culture Media; D004917:Erythromycin; D010770:Phosphotransferases; D003065:Coenzyme A