Physically Discrete β-Lactamase-Type Thioesterase Catalyzes Product Release in Atrochrysone Synthesis by Iterative Type I Polyketide Synthase Original Research Article

ATEG_08451 in Aspergillus terreus, here named atrochrysone carboxylic acid synthase (ACAS), is a nonreducing, iterative type I polyketide synthase that contains no thioesterase domain. In vitro, reactions of ACAS with malonyl-CoA yielded a polyketide intermediate, probably attached to its acyl carrier protein (ACP). The addition of ATEG_08450, here named atrochrysone carboxyl ACP thioesterase (ACTE), to the reaction resulted in the release of products derived from atrochrysone carboxylic acid, such as atrochrysone and endocrocin. ACTE, belonging to the β-lactamase superfamily, thus appears to be a novel type of thioesterase responsible for product release in polyketide biosynthesis. These findings show that ACAS synthesizes the scaffold of atrochrysone carboxylic acid from malonyl-CoA, and that ACTE hydrolyzes the thioester bond between the ACP of ACAS and the intermediate to release atrochrysone carboxylic acid as the reaction product.