Ketoacylsynthases

Ketoacylsynthases, often abbreviated as KS, are a family of enzymes that play a crucial role in the biosynthesis of fatty acids and polyketides. They are central components of modular enzyme complexes known as fatty acid synthases (FAS) and polyketide synthases (PKS). The primary function of a ketoacylsynthase is to catalyze the condensation reaction between an acyl or acyl-CoA extender unit and a growing polyketide or fatty acid chain. This reaction involves the formation of a new carbon-carbon bond, extending the chain by two carbons derived from the extender unit.

Specifically, the KS domain within a FAS or PKS module is responsible for the decarboxylative Claisen condensation. It activates the extender unit, typically a malonyl-CoA derivative, and facilitates its attack on the thioester-bound chain of the preceding enzyme domain, often a thioesterase or another KS. This process releases carbon dioxide and forms a beta-ketoacyl intermediate. Subsequent domains within the PKS or FAS complex then modify this beta-ketoacyl intermediate through reduction and dehydration steps, leading to the saturated fatty acid or more complex polyketide product. The specificity of the KS domain dictates which extender units can be incorporated, contributing to the diversity of fatty acids and polyketides produced.