Complete Decoration of the Indolyl Residue in <i>cyclo</i>-<scp>l</scp>-Trp-<scp>l</scp>-Trp with Geranyl Moieties by Using Engineered Dimethylallyl Transferases

Abstract

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.