title: Potential rearrangements in the reaction catalyzed by the indole prenyltransferase FtmPT1.
abstract: The indole prenyltransferase FtmPT1 catalyzes the C-2 normal prenylation of brevianamide F (cyclo-L-Trp-L-Pro) to give tryprostatin B. A previous structural analysis and studies with alternate substrates suggest that the reaction might not proceed through a direct C-2 attack, but could involve a C-3 prenylation followed by a rearrangement. In this work we investigated the reactivity of FtmPT1 with tryptophan, 5-hydroxybrevianamide, and 2-methylbrevianamide, and isolated products that had been reverse prenylated at C-3 and normal prenylated at N-1, C-3, or C-4. The formation of these products can be rationalized through mechanisms involving either an initial C-3 normal or C-3 reverse prenylation. In addition, we demonstrate that a C-3 reverse prenylated indole can undergo a nonenzymatic aza-Cope rearrangement at 37 °C to give an N-1 normal prenylated product. Together, these studies broaden the known product scope of this interesting catalyst and suggest that alternative mechanisms might be operating.
authors.affiliation: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1 (Canada).
authors.forename: Niusha
authors.initials: N
authors.lastname: Mahmoodi
authors.forename: Martin E
authors.initials: ME
authors.lastname: Tanner
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000201:enzymology; D055162:Biocatalysis; D020134:Catalytic Domain; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D008958:Models, Molecular; D054876:Prenylation
chemical_list: D000470:Alkaloids; D007211:Indoles; D004122:Dimethylallyltranstransferase
keywords: alkaloids; indoles; prenyltransferases; reaction mechanisms; rearrangements