The Thioesterase of the Erythromycin-Producing Polyketide Synthase: Influence of Acyl Chain Structure on the Mode of Release of Substrate Analogues from the Acyl Enzyme Intermediates

The production of genetically engineered polyketides depends critically on thioesterase activity for product release. In vitro studies with the thioesterase from the erythromycin polyketide synthase (PKS) have demonstrated that the ability of this enzyme to act as a universal decoupler is limited, but stereochemical variation is readily tolerated. Synthetic analogues with all four stereochemical configurations of the natural substrate's 2-methyl-3-hydroxy substitution pattern ( 1 – 4 ; X=p-nitrophenoxy) were substrates for the enzyme.