DIVERGENT SEQUENCE MOTIFS CORRELATED WITH THE SUBSTRATE-SPECIFICITY OF (METHYL)MALONYL-COA-ACYL CARRIER PROTEIN TRANSACYLASE DOMAINS IN MODULAR POLYKETIDE SYNTHESES

The amino acid sequences of a large number of polyketide synthase doma ins that catalyse the transacylation of either methylmalonyl-CoA or ma lonyl-CoA onto acyl carrier protein (ACP) have been compared, Regions were identified in which the acyltransferase sequences diverged accord ing to whether they were specific for malonyl-CoA or methylmalonyl-CoA , These differences are sufficiently clear to allow unambiguous assign ment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the ma lonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase ac tive site, though not close enough to make direct contact with bound s ubstrate.