Regiospecific Benzylation of Tryptophan and Derivatives Catalyzed by a Fungal Dimethylallyl Transferase

A big challenge in organic synthesis is to reach a high regioselectivity. Enzymes catalyze usually highly regiospecific reactions and can function as ideal biocatalysts for such purposes. Some secondary metabolite enzymes can even use distinctly different unnatural substrates and expand therefore their potential usage in chemoenzymatic synthesis. We report here the acceptance of benzyl diphosphate as an alkyl donor by the fungal dimethylallyl transferase FgaPT2 and the regiospecific enzymatic benzylation of tryptophan and several analogues

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

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

Breaking Cyclic Dipeptide Prenyltransferase Regioselectivity by Unnatural Alkyl Donors

The behavior of five cyclic dipeptide prenyltransferases, responsible for C2-regular, C2-reverse, or C3-reverse prenylation, was investigated in the presence of the unnatural alkyl donors monomethylallyl and 2-pentenyl diphosphate. Both substrates were well accepted by the tested enzymes. Interestingly, C2-reverse and C3-reverse monoalkylated derivatives were identified as enzyme products in all of the enzyme assays. These findings indicate their similar reaction characteristics in the presence of unnatural alkyl donors