Expansion of Enzymatic Friedel–Crafts Alkylation on Indoles: Acceptance of Unnatural β‑Unsaturated Allyl Diphospates by Dimethylallyl-tryptophan Synthases

Abstract

Prenyltransferases of the dimethylallyl-tryptophan synthase (DMATS) superfamily catalyze Friedel–Crafts alkylation with high flexibility for aromatic substrates, but the high specificity for dimethylallyl diphosphate (DMAPP) prohibits their application as biocatalysts. We demonstrate here that at least one methyl group in DMAPP can be deleted or shifted to the δ-position. For acceptance by some DMATS enzymes, however, a double bond must be situated at the β-position. Furthermore, the alkylation position of an analogue can differ from that of DMAPP