Thioesterase 1 (TesA) (TesA)

Thioesterase TesA is a multifunctional enzyme found in various bacteria, most notably Escherichia coli and Mycobacterium tuberculosis (UniProt P0ADA1, P9WQD1). It belongs to the SGNH-hydrolase superfamily and possesses thioesterase, protease, arylesterase, and lysophospholipase activities (RCSB PDB 1J00). In M. tuberculosis, TesA is essential for the biosynthesis of complex cell wall lipids, such as phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), which are critical virulence factors that contribute to drug resistance and immune evasion (PubMed 30292819). Due to its role in maintaining cell wall integrity, TesA is considered a viable therapeutic target for the development of novel antitubercular drugs (PubMed 31388991). Small molecules like cyclophostin analogs and methyl arachidonyl fluorophosphonate have been identified as inhibitors that covalently bind to the enzyme's catalytic serine residue (PubMed 30292819). Inhibition of TesA leads to decreased lipid production and enhances the efficacy of other antibiotics, such as vancomycin, by increasing cell wall permeability (PubMed 31388991). Research into TesA also extends to metabolic engineering, where it is utilized to optimize the microbial production of fatty acids and biofuels (MDPI 2022).

Other names

Protease 1Lysophospholipase L1Thioesterase IAcyl-CoA thioesterase 1TAPArylesteraseOleoyl-[acyl-carrier-protein] hydrolaseapeApldC

Covalent inhibition of the catalytic serine residue