Complete Decoration of the Indolyl Residue in cyclo-l‑Trp‑l‑Trp with Geranyl Moieties by Using Engineered Dimethylallyl Transferases

Mutation of the gatekeeping residues for prenyl donor selectivity in six dimethylallyl transferases significantly increased their activities toward geranyl diphosphate. Forty-two geranylated derivatives were obtained from 15 cyclic dipeptides by using the engineered enzymes. Taking cyclo-l-Trp-l-Trp as an example, the geranyl moiety can be attached to all seven possible positions of the indole nucleus. This study demonstrates a convenient way to increase the structural diversity of geranylated products by structure-based engineering of the available dimethylallyl transferases.