7e5v

Structural highlights

Function

PHM7_PYRSX Diels-Alderase; part of the gene cluster that mediates the biosynthesis of the trans-fused decalin-containing tetramic acid phomasetin, the stereochemical opposite of the HIV-1 integrase inhibitor equisetin (PubMed:29972614). The PKS module of phm1 together with the enoylreductase phm4 catalyze the formation of the polyketide unit which is then conjugated to L-serine by the condensation domain of the phm1 NRPS module (PubMed:29972614). Activity of the Dieckmann cyclase domain (RED) of phm1 results in release of the Dieckmann product intermediate (PubMed:29972614). The Diels-Alderase phm7 then uses the Dieckmann product of phm1 as substrate and catalyzes the Diels-Alder cycloaddition to form the decalin ring of N-desmethylphomasetin (PubMed:29972614, PubMed:34121297). N-desmethylphomasetin is further methylated to phomasetin by the methyltransferase phm5 (PubMed:29972614).^{[1] [2]}

References

1. ↑ Kato N, Nogawa T, Takita R, Kinugasa K, Kanai M, Uchiyama M, Osada H, Takahashi S. Control of the Stereochemical Course of [4+2] Cycloaddition during trans-Decalin Formation by Fsa2-Family Enzymes. Angew Chem Int Ed Engl. 2018 Jul 26;57(31):9754-9758. PMID:29972614 doi:10.1002/anie.201805050
2. ↑ Fujiyama K, Kato N, Re S, Kinugasa K, Watanabe K, Takita R, Nogawa T, Hino T, Osada H, Sugita Y, Takahashi S, Nagano S. Molecular basis for two stereoselective Diels-Alderases that produce decalin skeletons. Angew Chem Int Ed Engl. 2021 Jun 13. doi: 10.1002/anie.202106186. PMID:34121297 doi:http://dx.doi.org/10.1002/anie.202106186