Production of diprenylated indole derivatives by tandem incubation of two recombinant dimethylallyltryptophan synthases
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Production of diprenylated indole derivatives by tandem incubation of two recombinant dimethylallyltryptophan synthases Han-Li Ruan Æ Edyta Stec Æ Shu-Ming Li
Received: 20 June 2009 / Revised: 30 July 2009 / Accepted: 16 August 2009 / Published online: 1 September 2009 Ó Springer-Verlag 2009
Abstract Two dimethylallyltryptophan synthases, FgaPT2 and 7-DMATS, which catalysed the prenylation of L-tryptophan at positions C4 and C7, respectively, have been recently identified in Aspergillus fumigatus and proven biochemically. These enzymes were successfully used for the production of monoprenylated indole derivatives. In this study, we showed that C4,C7-diprenylated indole derivatives, e.g. 4,7-di-(dimethylallyl)-L-tryptophan, 4,7di-(dimethylallyl)-L-abrine and 4,7-di-(dimethylallyl)-11methyltryptophan, could be conveniently produced by tandem incubation of both enzymes. The structures of the isolated enzymatic products were elucidated by NMR and MS analyses. High conversion yields of up to 93% were achieved by an incubation sequence of FgaPT2 followed by 7-DMATS. The results reported in this study demonstrated the potential of secondary metabolite enzymes as promising tools for the production of designed compounds.
Communicated by Axel Brakhage.
Electronic supplementary material The online version of this article (doi:10.1007/s00203-009-0504-9) contains supplementary material, which is available to authorized users. H.-L. Ruan E. Stec S.-M. Li (&) Philipps-Universita¨t Marburg, Institut fu¨r Pharmazeutische Biologie, Deutschhausstraße 17a, 35037 Marburg, Germany e-mail: [email protected] H.-L. Ruan Faculty of Pharmacy, Tongji Medical College and Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Huazhong University of Science and Technology, Hangkong Road 13, 430030 Wuhan, China
Keywords Aspergillus fumigatus Chemoenzymatic synthesis Dimethylallyltryptophan synthase Prenylated indole derivatives Prenyltransferase and prenylation Abbreviations DMA Dimethylallyl DMAPP Dimethylallyl diphosphate DMAT Dimethylallyltryptophan DMATS Dimethylallyltryptophan synthase
Introduction Chemoenzymatic synthesis or enzyme-catalysed chemical transformations by using purified enzymes are now widely recognized as practical alternatives to traditional organic synthesis and as convenient solutions to certain intractable synthetic problems (Koeller and Wong 2001). By using this strategy, we have synthesized different prenylated simple indole derivatives or tryptophan-containing cyclic dipeptides by in vitro prenylation with recombinant fungal prenyltransferases, which are involved in the biosynthesis of diverse secondary metabolites (Steffan et al. 2009). For example, the two dimethylallyltryptophan synthases, FgaPT2 and 7-DMATS, which catalysed the prenylation of L-tryptophan at positions C4 and C7 (Kremer et al. 2007; Unso¨ld and Li 2005), respectively, showed also flexibility towards their aromatic substrates. Previous studies (Kremer and Li 2008; Steffan et al.
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