title: Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A.
abstract: SpnF, an enzyme involved in the biosynthesis of spinosyn A, catalyzes a transannular Diels-Alder reaction. Quantum mechanical computations and dynamic simulations now show that this cycloaddition is not well described as either a concerted or stepwise process, and dynamical effects influence the identity and timing of bond formation. The transition state for the reaction is ambimodal and leads directly to both the observed Diels-Alder and an unobserved [6+4] cycloadduct. The potential energy surface bifurcates and the cycloadditions occur by dynamically stepwise modes featuring an "entropic intermediate". A rapid Cope rearrangement converts the [6+4] adduct into the observed [4+2] adduct. Control of nonstatistical dynamical effects may serve as another way by which enzymes control reactions.
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095-1569, United States.
authors.forename: Ashay
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Chemistry, Texas A & M University , College Station, Texas 77843-3255, United States.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095-1569, United States.
authors.forename: Zhongyue
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095-1569, United States.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Gutiérrez
authors.affiliation: College of Pharmacy and Department of Chemistry, University of Texas at Austin , Austin, Texas 78712-1224, United States.
authors.forename: Hung-wen
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095-1569, United States.
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.affiliation: Department of Chemistry, Texas A & M University , College Station, Texas 77843-3255, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Singleton
mesh_terms: D061565:Cycloaddition Reaction; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D018942:Macrolides; C114883:spinosyn A