3-Ketoacyl-coenzyme A thiolase (KAT)

3-Ketoacyl-coenzyme A thiolase (KAT) is an enzyme from the thiolase superfamily that catalyzes the thiolytic cleavage of 3-ketoacyl-CoA into acetyl-CoA and a shortened fatty acyl-CoA, representing the last step in the beta-oxidation of fatty acids in mitochondria and peroxisomes. KAT can also catalyze the reverse Claisen condensation reaction, enabling the carbon chain elongation of acyl-CoAs, which is exploited for synthetic biology and metabolic engineering, including bioproduction of value-added chemicals such as adipic acid and polyhydroxyalkanoates. There are isoforms in both mitochondria and peroxisomes, and deficiencies in these can result in inherited metabolic disorders characterized by disruption in fatty acid oxidation, leading to hypoketotic hypoglycemia and organ dysfunction. KAT is not a target of any approved therapeutic drugs but plays a crucial role in metabolic engineering and has been proposed as a drug discovery target for modulating fatty acid metabolism.

Other names

3-ketoacyl-CoA thiolaseThiolase IKetoacyl-CoA thiolase3-oxoacyl-CoA thiolaseKATMCKAT (medium-chain variant)

Catalysis of thiolytic cleavage of 3-ketoacyl-CoA to acetyl-CoA and fatty acyl-CoA Claisen condensation of two acyl-CoA substrates for carbon chain elongation