Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

Aromatic prenyltransferases (PTases) are enzymes that catalyze Friedel-Crafts reactions between aromatic compounds and isoprenoid diphosphates. In hapalindole biosynthesis, the aromatic PTases AmbP1 and AmbP3 exhibit surprisingly plastic selectivities. AmbP1 not only transfers the geranyl group on the C-3 of cis-indolylvinyl isonitrile, but also on the C-2, which is supressed in the presence of Mg²⁺ ions. AmbP3 transfers the dimethylallyl group on C-2 of hapalindole U in the reverse manner, but on C-2 of its C-10 stereoisomer in the normal manner. This review highlights the molecular bases of the AmbP1 and AmbP3 functions, elucidated through their X-ray crystal structures. The knowledge presented here will contribute to the understanding of aromatic PTase reactions and will enhance their uses as biocatalysts.