Increasing structure diversity of prenylated diketopiperazine derivatives by using a 4-dimethylallyltryptophan synthase.
To create structural diversity of prenylated diketopiperazine derivatives, acceptance of cyclic dipeptides was tested using FgaPT2, a prenyltransferase from Aspergillus fumigatus, which catalyses the conversion of L: -tryptophan to 4-dimethylallyl-L: -tryptophan. It could be shown that seven tryptophan-containing cyclic dipeptides were accepted by FgaPT2 at high protein concentrations and regiospecifically converted to their C4 prenylated derivatives. The structures of the enzymatic products were elucidated by NMR and LC-MS analyses. This substrate promiscuity of a dimethylallyltryptophan synthase towards cyclic dipeptides increases the potential of the fungal indole prenyltransferases as tools for the production of biologically active compounds.
Steffan
Nicola
N
Institut für Pharmazeutische Biologie, Philipps-Universität Marburg, Deutschhausstrasse 17A, Marburg, Germany. nicola.steffan@staff.uni-marburg.de
Li
Shu-Ming
SM
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000201:enzymology*; D002853:Chromatography, Liquid; D054659:Diketopiperazines / Q000737:chemistry* / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010456:Peptides, Cyclic / Q000378:metabolism
D054659:Diketopiperazines; D004151:Dipeptides; D005656:Fungal Proteins; D010456:Peptides, Cyclic; D019883:Alkyl and Aryl Transferases; C032409:tryptophan dimethylallyltransferase