6jjt
From Proteopedia
Crystal structure of an enzyme from Penicillium herquei in condition1
Structural highlights
FunctionPHNH_PENHR Hydroalkoxylation enzyme; part of the gene cluster that mediates the biosynthesis of phenalenones such as herqueinone, compounds that have been reported to treat tumors, bacterial infections and/or mycoses, and rheumatic diseases (PubMed:26978228). The non-reducing polyketide synthase phnA synthesizes the heptaketide backbone and cyclizes it into the angular, hemiketal-containing naphtho-gamma-pyrone prephenalenone. The product template (PT) domain of phnA catalyzes only the C4-C9 aldol condensation, which is unprecedented among known PT domains (PubMed:28240554, PubMed:26978228). The transformation of prephenalenone to phenalenones requires an FAD-dependent monooxygenase phnB, which catalyzes the C2 aromatic hydroxylation of prephenalenone and ring opening of the gamma-pyrone ring simultaneously (PubMed:28240554, PubMed:26978228). Subsequent intramolecular deprotonation of C3 phenolic oxygen accelerates phenalenone ring closure to yield the tricyclic phenalenone core with a C2 hydroxylation (PubMed:28240554, PubMed:26978228). The prenyltransferase phnF further catalyzes reverse C-prenylation of phenalenone by direct electrophilic substitution at C6, or possibly via first a forward O-prenylation of a neighboring phenol in phenalenone, followed by a Claisen rearrangement (PubMed:28240554). The hydroalkoxylation enzyme phnH catalyzes the 5-exo-trigcyclization via acid catalysis after the spontaneous deprotonation of 7-OH, which leads to the formation of the dihydrobenzofuran atrovenetin (PubMed:28240554). Atrovenetin is further converted to deoxyherqueinone by the O-methyltransferase phnC which can methylate C2-OH to stabilize the northern portion of the phenalenone core (PubMed:28240554). Finally, the oxidoreductase phnG converts deoxyherqueinone to herqueinone via C6 hydroxylation (PubMed:28240554).[1] [2] Publication Abstract from PubMedHydroalkoxylation is a useful and efficient reaction which generates C-O bond and produces cyclic ethers, the common structural elements of natural products. The dedicative enzyme which can catalyze enantioselective hydroalkoxylation named PhnH was recently identified in the herqueinone biosynthetic gene from Penicillium herquei. It catalyzes addition of a phenol to the terminal olefin on substrate to produce a dihydrobenzofuran. Here, the crystal structure of PhnH is reported and the putative substrate-binding pocket is illustrated. Through docking experiment, possible substrate-binding poses are displayed and the catalytic mechanism is therefore proposed. Our findings form the basis for further studies of enantioselective hydroalkoxylation enzymes. Crystal structure and proposed mechanism of an enantioselective hydroalkoxylation enzyme from Penicillium herquei.,Feng Y, Yu X, Huang JW, Liu W, Li Q, Hu Y, Yang Y, Chen Y, Jin J, Li H, Chen CC, Guo RT Biochem Biophys Res Commun. 2019 Aug 27;516(3):801-805. doi:, 10.1016/j.bbrc.2019.06.100. Epub 2019 Jun 27. PMID:31256936[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Penicillium herquei | Chen CC | Fen Y | Guo RT | Huang JW | Liu WD
