title: Enzyme-Catalyzed Intramolecular Enantioselective Hydroalkoxylation.
abstract: Hydroalkoxylation is a powerful and efficient method of forming C-O bonds and cyclic ethers in synthetic chemistry. In studying the biosynthesis of the fungal natural product herqueinone, we identified an enzyme that can perform an intramolecular enantioselective hydroalkoxylation reaction. PhnH catalyzes the addition of a phenol to the terminal olefin of a reverse prenyl group to give a dihydrobenzofuran product. The enzyme accelerates the reaction by 3 × 105-fold compared to the uncatalyzed reaction. PhnH belongs to a superfamily of proteins with a domain of unknown function (DUF3237), of which no member has a previously verified function. The discovery of PhnH demonstrates that enzymes can be used to promote the enantioselective hydroalkoxylation reaction and form cyclic ethers.
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Shu-Shan
authors.initials: SS
authors.lastname: Gao
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Marc
authors.initials: M
authors.lastname: Garcia-Borràs
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Joyann S
authors.initials: JS
authors.lastname: Barber
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Yang
authors.identifier: 0000-0002-2039-5367
authors.initials: Y
authors.lastname: Hai
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Abing
authors.initials: A
authors.lastname: Duan
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Neil K
authors.identifier: 0000-0002-7793-2629
authors.initials: NK
authors.lastname: Garg
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: K N
authors.identifier: 0000-0002-8387-5261
authors.initials: KN
authors.lastname: Houk
authors.affiliation: Department of Chemical and Biomolecular Engineering and ⊥Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Yi
authors.identifier: 0000-0003-1597-0141
authors.initials: Y
authors.lastname: Tang
mesh_terms: D055162:Biocatalysis; D008190:Lyases / Q000378:metabolism*; D015394:Molecular Structure; D043803:Phenalenes / Q000378:metabolism*; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D043803:Phenalenes; D008190:Lyases; C030464:herquienone