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

Org Biomol Chem. 2012 Dec 14;10(46):9262-70. doi: 10.1039/c2ob26149a. Epub 2012 Oct 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus fumigatus / chemistry
  • Aspergillus fumigatus / enzymology*
  • Chromatography, High Pressure Liquid
  • Dimethylallyltranstransferase / chemistry*
  • Dimethylallyltranstransferase / isolation & purification
  • Escherichia coli / genetics
  • Hemiterpenes / chemistry*
  • Indoles / chemistry*
  • Magnetic Resonance Spectroscopy
  • Organophosphorus Compounds / chemistry*
  • Peptides, Cyclic / chemistry*
  • Prenylation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Spectrometry, Mass, Electrospray Ionization
  • Stereoisomerism
  • Substrate Specificity


  • Hemiterpenes
  • Indoles
  • Organophosphorus Compounds
  • Peptides, Cyclic
  • Recombinant Proteins
  • 3,3-dimethylallyl pyrophosphate
  • Dimethylallyltranstransferase
  • FtmPT1 protein, Aspergillus fumigatus