5yy2

Structural highlights

Function

ASQI_EMENI Cyclopenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:30026518). Within the pathway, the cyclopenase asqI catalyzes the conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin (PubMed:30026518). Cyclopenin can also be converted into viridicatin by asqI (PubMed:30026518). The first step of the pathway is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin. 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ. AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin. The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin is catalyzed by the cyclopenase asqI. 4'-methoxyviridicatin is the precursor of quinolone natural products, and is further converted to quinolinone B. The prenyltransferase asqH1 then catalyzes the canonical Friedel-Crafts alkylation of quinolinone B with dimethylallyl cation to yield dimethylallyl quinolone, which is subjected to FAD-dependent dehydrogenation by the FAD-linked oxidoreductase asqF to yield conjugated aryl diene. The delta(3') double bond then serves as the site of the second alkylation with DMAPP catalyzed by the prenyltransferase asqH2 to yield a carbenium ion intermediate, which can be attacked by H(2)O to yield a styrenyl quinolone containing a C3'-hydroxyprenyl chain. The FAD-dependent monooxygenase asqG performs epoxidation of the terminal C7'-C8' olefin. Finally, after dehydratation of the epoxide at C3 by asqC, the quinolone epoxide rearrangement protein asqO catalyzes an enzymatic 3-exo-tet cyclization to yield the cyclopropyl-THF ring system in aspoquinolone (Probable).^{[1] [2]}

References

1. ↑ Ishikawa N, Tanaka H, Koyama F, Noguchi H, Wang CC, Hotta K, Watanabe K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew Chem Int Ed Engl. 2014 Nov 17;53(47):12880-4. doi: 10.1002/anie.201407920. , Epub 2014 Sep 22. PMID:25251934 doi:http://dx.doi.org/10.1002/anie.201407920
2. ↑ Kishimoto S, Hara K, Hashimoto H, Hirayama Y, Champagne PA, Houk KN, Tang Y, Watanabe K. Enzymatic one-step ring contraction for quinolone biosynthesis. Nat Commun. 2018 Jul 19;9(1):2826. doi: 10.1038/s41467-018-05221-5. PMID:30026518 doi:http://dx.doi.org/10.1038/s41467-018-05221-5