title: Biological matching of chemical reactivity: pairing indole nucleophilicity with electrophilic isoprenoids.
abstract: The indole side chain of tryptophan has latent nucleophilic reactivity at both N1 and all six (nonbridgehead) carbons, which is not generally manifested in post-translational reactions of proteins. On the other hand, all seven positions can be prenylated by the primary metabolite Δ(2)-isopentenyl diphosphate by dimethyallyl transferase (DMATs) family members as initial steps in biosynthetic pathways to bioactive fungal alkaloids including ergots and tremorgens. These are formulated as regioselective capture of isopentenyl allylic cationic transition states by the indole side chain as a nucleophile. The balance of regiospecificity and promiscuity among these indole prenyltransferases continues to raise questions about possible Cope and azaCope rearrangements of nascent products. In addition to these two electron reaction manifolds, there is evidence for one electron reaction manifolds in indole ring biosynthetic functionalization.
authors.affiliation: ChEM-H Institute and Department of Chemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D004122:Dimethylallyltranstransferase / Q000378:metabolism*; D004876:Ergot Alkaloids / Q000096:biosynthesis / Q000737:chemistry; D005656:Fungal Proteins / Q000378:metabolism*; D005658:Fungi / Q000378:metabolism; D045782:Hemiterpenes / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism; D054876:Prenylation; D013237:Stereoisomerism; D013379:Substrate Specificity; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004876:Ergot Alkaloids; D005656:Fungal Proteins; D045782:Hemiterpenes; D007211:Indoles; D009943:Organophosphorus Compounds; D013729:Terpenes; C004809:isopentenyl pyrophosphate; D014364:Tryptophan; D019883:Alkyl and Aryl Transferases; D004122:Dimethylallyltranstransferase; C032409:tryptophan dimethylallyltransferase