Regioselective Biocatalytic C4-Prenylation of Unprotected Tryptophan Derivatives

Bettina Eggbauer, Joerg H. Schrittwieser, Bianca Kerschbaumer, Peter Macheroux, Wolfgang Kroutil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Regioselective carbon−carbon bond formation belongs to the challenging tasks in organic synthesis. In this context, C−C bond formation catalyzed by 4-dimethylallyltryptophan synthases (4-DMATSs) represents a possible tool to regioselectively synthesize C4-prenylated indole derivatives without site-specific preactivation and circumventing the need of protection groups as used in chemical synthetic approaches. In this study, a toolbox of 4-DMATSs to produce a set of 4-dimethylallyl tryptophan and indole derivatives was identified. Using three wild-type enzymes as well as variants, various C5-substituted tryptophan derivatives as well as N-methyl tryptophan were successfully prenylated with conversions up to 90 %. Even truncated tryptophan derivatives like tryptamine and 3-indole propanoic acid were regioselectively prenylated in position C4. The acceptance of C5-substituted tryptophan derivatives was improved up to 5-fold by generating variants (e. g. T108S). The feasibility of semi-preparative prenylation of selected tryptophan derivatives was successfully demonstrated on 100 mg scale at 15 mM substrate concentration, allowing to reduce the previously published multistep chemical synthetic sequence to just a single step.

Original languageEnglish
Article numbere202200311
JournalChemBioChem
Volume23
Issue number17
DOIs
Publication statusPublished - 5 Sept 2022

Keywords

  • biocatalysis
  • C−C bond formation
  • prenylation
  • protein engineering
  • regioselectivity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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