Biochemical characterization of a malonyl-specific acyltransferase domain of FK506 biosynthetic polyketide synthase.

Acyltransferases (ATs) play an essential role in the polyketide biosynthesis through transferring acyl units into acyl carrier proteins (ACPs) via a self-acylation reaction and a transacylation reaction. Here we used AT10(FkbA) of FK506 biosynthetic polyketide synthase (PKS) from Streptomyces tsukubaensis YN06 as a model to study the specificity of ATs for acyl units. Our results show that AT10(FkbA) can form both malonyl-O-AT10(FkbA) and methylmalonyl-O-AT10(FkbA) in the self-acylation reaction, however, only malonyl-O-AT10FkbA but not methylmalonyl-O-AT10(FkbA) can transfer the acyl unit into ACPs in the transacylation reaction. Unlike some ATs that are known to control the acyl specificity in self-acylation reactions, AT10(FkbA) controls the acyl specificity in transacylation reactions.