Four Amino Acid Residues in Acyltransferase Affect the Production of Epothilone A to Mixed Epothilones A and B

Abstract Surveying more than 100 native epothilone producing strains were isolated from different locales revealed that the production ratio of epothilones A and B was sorted into two groups, almost single epothilone A or approximate 2:1 ratio of A and B. Sequencing the second acyltransferase in the epoC module (AT ModC2 ) of different Sorangium producers indicated that four amino acid residues at sites 90, 91, 95 and 196 in the enzyme active centre altered in parallel to the production ratio shift. In those producers with single epothilone A, AT ModC2 had almost the same sequence and computational structure as AT ModC1 , which selectively accepts malonyl-CoA as the extender units.