Family

Thioesterase type II, NRPS/PKS/S-FAS (IPR012223)

Short name: TEII

Family relationships

Description

This family contains thioesterases involved in non-ribosomal peptide biosynthesis or polyketide biosynthesis, as well as those involved in vertebrate fatty acid biosynthesis (medium-chain S-acyl fatty acid synthase thioesterases, EC:3.1.2.14). Based on domain architecture, they belong to type II (stand-alone, non-integrated) thioesterases (TEII). Based on the structural fold, they belong to the thioesterases of the alpha/beta hydrolase fold. This group of thioesterases is distantly related to the integrated (type I) thioeterases that are intrinsic components of animal fatty acid synthase and in this context serve to terminate chain elongation.

Prokaryotic members of this family are involved in non-ribosomal peptide biosynthesis or polyketide biosynthesis. Type I polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are organised into modules, each adding one fatty acid or amino acid substrate to a growing chain [PMID: 10508662]. Synthetic intermediates are covalently tethered by thioester linkages to a carrier protein domain in each module. Cyclization and release of the product is catalysed by the type I thioesterase (TEI) which is usually fused C-terminally to the last module (integrated) [PMID: 11001063, PMID: 10508662, PMID: 12416979, PMID: 12005429, PMID: 11401555]. In most systems, another component, type II thioesterase, represented by this family, is also present. For example, SrfTE is a TEI domain embedded at the downstream end of the final subunit, SrfC [PMID: 12005429], and SrfA-TE is a stand-alone TEII [PMID: 9560421]. These enzymes are not essential; however, they are important for effective synthesis, because deletion of the genes leads to a drastic reduction in product yields [PMID: 9560421]. TEII enzymes that are associated with the synthetases of the peptide antibiotics surfactin (TEIIsrf) and bacitracin (TEIIbac) were shown to efficiently regenerate miss-acylated thiol groups of 4 -phosphopantetheine (4 PP) cofactors attached to the peptidyl carrier proteins (PCPs) of NRPSs [PMID: 12384573]. Therefore, the role of TEIIs in non-ribosomal peptide synthesis is the regeneration of miss-acylated NRPSs, which result from the apo to holo conversion of NRPS enzymes because of the promiscuity of dedicated 4 PP transferases that use not only free CoA, but also acyl-CoAs as 4 PP donors [PMID: 12384573].

Members of this family from vertebrates are medium-chain S-acyl fatty acid synthase thioesterases (TEII, EC:3.1.2.14). They are tissue-specific (found in mammary glands of nonruminants and uropygial glands of waterfowl) chain-terminating enzymes of the fatty acid biosynthesis pathway for the synthesis of shorter chain fatty acids instead of palmitic acid as the major product. TEIIs are stand-alone enzymes that interact with the fatty acid synthase complex and catalyse premature release of the growing acyl chain [PMID: 2318831, PMID: 3968077].

Thioesterases are classified into two structural classes: those with a classical alpha/beta hydrolase fold, containing a classic Ser-His-Asp triad in the active site [PMID: 11080636], and those with a "hot dog" fold [PMID: 8805534] (e.g., IPR003703, PIRSF003230, PIRSF016607, etc). Typically, those of the former class act on acylated proteins (Acyl-ACP etc), while those of the latter class act on CoA thioesters. Members of this family, as well as related integrated non-ribosomal peptide/polyketide biosynthesis thioesterases (e.g., PIRSF001610) and FAS thioesterases (PIRSF000453), belong to the alpha/beta hydrolase fold class [PMID: 12005429].

Nomenclature note: In the Escherichia coli nomenclature, there are thioesterase I (TesA) and thioesterae II (TesB, IPR003703) enzymes. This nomenclature is not derived from the type I and type II classification based on domain architecture (note that both TesA and TesB are stand-alone thioesterases). Therefore, the term TEII is being used by different authors either as a reference to the stand-alone type TE or as a reference to the TesB group, or both.

GO terms

Biological Process

GO:0009058 biosynthetic process

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER