title: Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis.
abstract: Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.
authors.affiliation: Department of Biological Sciences, National University of Singapore , 117543 Singapore.
authors.forename: Fong T
authors.initials: FT
authors.lastname: Wong
authors.forename: Kinya
authors.initials: K
authors.lastname: Hotta
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Minyi
authors.initials: M
authors.lastname: Fang
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Chu-Young
authors.initials: CY
authors.lastname: Kim
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D003500:Cyclization; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D004987:Ethers / Q000737:chemistry / Q000378:metabolism*; D007832:Lasalocid / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001688:Biological Products; D004987:Ethers; D011108:Polymers; D004851:Epoxide Hydrolases; D007832:Lasalocid