title: P450-Mediated Coupling of Indole Fragments To Forge Communesin and Unnatural Isomers.
abstract: Dimeric indole alkaloids are structurally diverse natural products that have attracted significant attention from the synthetic and biosynthetic communities. Here, we describe the characterization of a P450 monooxygenase CnsC from Penicillium that catalyzes the heterodimeric coupling between two different indole moieties, tryptamine and aurantioclavine, to construct vicinal quaternary stereocenters and yield the heptacyclic communesin scaffold. We show, via biochemical characterization, substrate analogues, and computational methods that CnsC catalyzes the C3-C3' carbon-carbon bond formation and controls the regioselectivities of the pair of subsequent aminal bond formations to yield the communesin core. Use of ω-N-methyltryptamine and tryptophol in place of tryptamine led to the enzymatic synthesis of isocommunesin compounds, which have not been isolated to date.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Travis C
authors.initials: TC
authors.lastname: McMahon
authors.forename: Ashay
authors.initials: A
authors.lastname: Patel
authors.forename: Michael
authors.initials: M
authors.lastname: Corsello
authors.forename: Adam
authors.initials: A
authors.lastname: Simon
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Muxun
authors.initials: M
authors.lastname: Zhao
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: Neil K
authors.initials: NK
authors.lastname: Garg
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007536:Isomerism; D015394:Molecular Structure
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; C522026:communesin A; C030374:indole; D003577:Cytochrome P-450 Enzyme System