The thiolase superfamily: condensing enzymes with diverse reaction specificities

Trends Biochem Sci. 2006 Jan;31(1):64-71. doi: 10.1016/j.tibs.2005.11.011. Epub 2005 Dec 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases / metabolism*
  • Animals
  • Catalysis
  • Humans
  • Kinetics
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Secondary
  • Substrate Specificity
  • Thiosulfates / metabolism


  • Thiosulfates
  • Acyltransferases