The thiolase superfamily: condensing enzymes with diverse reaction specificities

Abstract

The formation of a carbon-carbon bond is an essential step in the biosynthetic pathways by which fatty acids and polyketides are made. The thiolase superfamily enzymes catalyse this carbon-carbon-bond formation via a thioester-dependent Claisen-condensation-reaction mechanism. In this way, fatty-acid chains and polyketides are made by sequentially adding simple building blocks, such as acetate units, to the growing molecule. A common feature of these enzymes is a reactive cysteine residue that is transiently acylated in the catalytic cycle. The wide catalytic diversity of the thiolase superfamily enzymes is of great interest. In particular, the type-III polyketide synthases make complicated compounds of great biological importance using multiple, subsequent condensation reactions, which are all catalysed in the same active-site cavity. The crucial metabolic importance of the bacterial fatty-acid-synthesizing enzymes stimulates in-depth studies that aim to develop efficient anti-bacterial drugs.