An acyltransferase domain of FK 506 polyketide synthase recognizing both an acyl carrier protein and coenzyme A as acyl donors to transfer allylmalonyl and ethylmalonyl units

Acyltransferase ( AT ) domains of polyketide synthases ( PKS s) usually use coenzyme A (CoA) as an acyl donor to transfer common acyl units to acyl carrier protein ( ACP ) domains, initiating incorporation of acyl units into polyketides. Two clinical immunosuppressive agents, FK 506 and FK 520, are biosynthesized by the same PKS s in several Streptomyces strains. In this study, characterization of AT 4 FkbB (the AT domain of the fourth module of FK 506 PKS ) in transacylation reactions showed that AT 4 FkbB recognizes both an ACP domain ( ACP T csA ) and CoA as acyl donors for transfer of a unique allylmalonyl ( AM ) unit to an acyl acceptor ACP domain ( ACP 4 FkbB ), resulting in FK 506 production. In addition, AT 4 FkbB uses CoA as an acyl donor to transfer an unusual ethylmalonyl ( EM ) unit to ACP 4 FkbB , resulting in FK 520 production, and transfers AM units to non‐native ACP acceptors. Characterization of AT 4 FkbB in self‐acylation reactions suggests that AT 4 FkbB controls acyl unit specificity in transacylation reactions but not in self‐acylation reactions. Generally, AT domains of PKS s only recognize one acyl donor; however, we report here that AT 4 FkbB recognizes two acyl donors for the transfer of different acyl units. Database Nucleotide sequence data have been submitted to the GenBank database under accession numbers KJ000382 and KJ000383 .