Structural highlights
Function
CGHA_CHAGB Diels-Alderase; part of the gene cluster that mediates the biosynthesis of the tetramic acid Sch210972, a potential anti-HIV fungal natural product that contains a decalin core (PubMed:26360642). The PKS module of cghG together with the enoylreductase cghC catalyze the formation of the polyketide unit which is then conjugated to 4-hydroxyl-4-methyl glutamate (HMG) by the condensation domain of the cghG NRPS module (PubMed:26360642). One unique structural feature of Sch210972 is the tetramic acid motif proposed to be derived from the non-proteinogenic amino acid HMG, by a Dieckmann-type condensation catalyzed by the reductase domain of cghG (PubMed:26360642). The aldolase cghB catalyzes the aldol condensation of 2 molecules of pyruvic acid to yield the intermediate 4-hydroxyl-4-methyl-2-oxoglutarate (HMOG), which can then be stereoselectively transaminated by an unidentified enzyme to form HMG (PubMed:26360642). The Diels-Alderase cghA then uses the Dieckmann product released by cghG as substrate and catalyzes the Diels-Alder cycloaddition to form the decalin ring of Sch210972 (PubMed:26360642). CghA also suppresses the nonenzymatic formation of the alternative stereoisomer (PubMed:26360642).[1]
References
- ↑ Sato M, Yagishita F, Mino T, Uchiyama N, Patel A, Chooi YH, Goda Y, Xu W, Noguchi H, Yamamoto T, Hotta K, Houk KN, Tang Y, Watanabe K. Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition. Chembiochem. 2015 Nov 2;16(16):2294-8. PMID:26360642 doi:10.1002/cbic.201500386
