Classification of Ketoacyl Synthases by Their Primary and Tertiary Structures

Ketoacyl synthases (KSs) are enzymes that catalyze the condensation of malonyl-acyl carrier protein (ACP) or malonyl-CoA with acyl-ACP or acyl-CoA units. This condensation reaction adds two carbon atoms to the acyl chain, and it is a key step in the fatty acid synthesis cycle. Our classification of KSs according to their primary and tertiary structures provides some insights into this enzyme group, as the KSs in each family have the same catalytic residues, mechanisms, and similar tertiary structures. Phylogenetic analysis of all families has been done to separate them into subfamilies for further study. At present, there are five KS families. KS1 members, overwhelmingly named β-ketoacyl-ACP III or its variants, are produced predominantly by bacteria. Members of KS2 are mainly produced by plants, and they are usually long-chain fatty acid elongases/condensing enzymes and 3-ketoacyl-CoA synthases. KS3, a very large family, is composed of bacterial and eukaryotic β-ketoacyl-ACP synthases I and II, often found in multidomain fatty acid and polyketide synthases. Most of the chalcone synthases, stilbene synthases, and naringenin-chalcone synthases in KS4 are from eukaryota. KS5 members are all from eukaryota, most are produced by animals, and they are mainly very long chain fatty acid elongases. KS sequences, tertiary structures, and family classifications are available on the continuously updated ThYme (Thioester-active Enzyme) database.