title: Breaking the regioselectivity of indole prenyltransferases: identification of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of the regular C2-prenyltransferase FtmPT1.
abstract: The prenyltransferase FtmPT1 from Aspergillus fumigatus is involved in the biosynthesis of fumitremorgin-type alkaloids and catalysed the regular C2-prenylation of brevianamide F (cyclo-L-Trp-L-Pro). It has been shown that FtmPT1 also accepted a number of other tryptophan-containing cyclic dipeptides and prenylated them, in the presence of dimethylallyl diphosphate, at C-2 of the indole nucleus. Detailed analysis of the incubation mixtures of FtmPT1 with these cyclic dipeptides revealed the presence of additional product peaks in the HPLC chromatograms. Seven regularly C3-prenylated hexahydropyrrolo[2,3-b]indoles were isolated and identified by HR-ESI-MS and NMR analyses including HMBC, HMQC and NOESY experiments. Further experiments proved that the C2- and C3-prenylated products are both independent enzyme products. To the best of our knowledge, this is the first report on the enzymatic formation of regularly C3-prenylated indolines. A reaction mechanism for both C2- and C3-prenylated derivatives was proposed.
authors.affiliation: Philipps-Universität Marburg, Institut für Pharmazeutische Biologie und Biotechnologie, Deutschhausstrasse 17A, D-35037 Marburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Wollinsky
authors.forename: Lena
authors.initials: L
authors.lastname: Ludwig
authors.forename: Xiulan
authors.initials: X
authors.lastname: Xie
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Li
mesh_terms: D001232:Aspergillus fumigatus / Q000737:chemistry / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004122:Dimethylallyltranstransferase / Q000737:chemistry* / Q000302:isolation & purification; D004926:Escherichia coli / Q000235:genetics; D045782:Hemiterpenes / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D054876:Prenylation; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D045782:Hemiterpenes; D007211:Indoles; D009943:Organophosphorus Compounds; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C043060:3,3-dimethylallyl pyrophosphate; D004122:Dimethylallyltranstransferase; C534854:FtmPT1 protein, Aspergillus fumigatus