title: Unified biogenesis of ambiguine, fischerindole, hapalindole and welwitindolinone: identification of a monogeranylated indolenine as a cryptic common biosynthetic intermediate by an unusual magnesium-dependent aromatic prenyltransferase.
abstract: Biochemical characterization of aromatic prenyltransferase AmbP1 and its close homologs WelP1/FidP1 in hapalindole-type alkaloid biosynthetic pathways is reported. These enzymes mediate the magnesium-dependent selective formation of 3-geranyl 3-isocyanovinyl indolenine (2) from cis-indolyl vinyl isonitrile and geranyl pyrophosphate. The role of the magnesium cofactor in AmbP1/WelP1/FidP1 catalysis is unusual for a microbial aromatic prenyltransferase, as it not only facilitates the formation of 2 but also prevents its rearrangement to an isomeric 2-geranyl 3-isocyanovinyl indole (3). The discovery of 2 as a cryptically conserved common biosynthetic intermediate to all hapalindole-type alkaloids suggests an enzyme-mediated Cope rearrangement and aza-Prins-type cyclization cascade is required to transform 2 to a polycyclic hapalindole-like scaffold.
authors.affiliation: Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA 15260, USA. xinyuliu@pitt.edu.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hillwig
authors.forename: Leonardus M I
authors.initials: LM
authors.lastname: Koharudin
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D004122:Dimethylallyltranstransferase / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D008345:Manganese; D004122:Dimethylallyltranstransferase