title: Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis.
abstract: Epoxides are highly useful synthons and biosynthons for the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a reaction that is notably missing, in regard to the synthetic toolbox, is cationic rearrangement that takes place under strong acid. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Marc
authors.identifier: 0000-0001-9458-1114
authors.initials: M
authors.lastname: Garcia-Borràs
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Mancheng C
authors.initials: MC
authors.lastname: Tang
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hirayama
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
authors.forename: Dehai H
authors.initials: DH
authors.lastname: Li
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.|Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry; D001233:Aspergillus nidulans / Q000201:enzymology; D055162:Biocatalysis; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010407:Penicillium / Q000201:enzymology; D011789:Quantum Theory; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D002412:Cations; D004852:Epoxy Compounds; D015363:Quinolones; D006836:Hydro-Lyases