Tryptophan C5-, C6- and C7-Prenylating Enzymes Displaying a Preference for C-6 of the Indole Ring in the Presence of Unnatural Dimethylallyl Diphosphate Analogues

The behavior of four dimethylallyltryptophan synthases (DMATSs) (5-DMATS and 5-DMATSSc as tryptophan C5-prenyltransferases, and 6-DMATSSa and 6-DMATSSv as C6-prenyltransferases) and one l-tyrosine prenyltransferase with a tryptophan C7-prenyltransferase activity was investigated in the presence of two unnatural alkyl donors (methylallyl and 2-pentenyl diphosphate) and one benzyl donor (benzyl diphosphate). Detailed biochemical investigations revealed the acceptance of these dimethylallyl diphosphate (DMAPP) analogues by all tested enzymes with different relative activities. Enzyme products with the allyl or benzyl moiety attached to different positions were identified in the reaction mixtures, whereby C-6 alkylated or benzylated l-tryptophan was found as one of the main products. This observation demonstrates a preference of the five prenyltransferases toward C-6 of the indole ring in the presence of unnatural DMAPP derivatives. Molecular dynamics simulation experiments with a homologous model of 5-DMATS explained well its reactions with methylallyl and 2-pentenyl diphosphate. Furthermore this study expands significantly the potential usage of tryptophan prenylating enzymes as biocatalysts for Friedel–Crafts alkylation.

Julia Winkelblech, Mike Liebhold, Jakub Gunera, Xiulan Xie, Peter Kolb, Shu-Ming Li

Advanced Synthesis & Catalysis

2015, 357, 975