A Single Amino Acid Switch Alters the Prenyl Donor Specificity of a Fungal Aromatic Prenyltransferase toward Biflavonoids

Biflavonoids are pharmaceutically important compounds. Prenylation usually improves bioactivity; however, prenylated biflavonoids are rare in nature. Here, we report successful prenylation or geranylation of biflavonoids using fungal prenyltransferase CdpC3PT and its mutants. F253 was identified as a key residue related to donor selectivity, which enables the switching from utilizing DMAPP to GPP precisely at the same C-3′′′ site of biflavonoids. Furthermore, another residue W181 was discovered to generally increase prenylation activity toward biflavonoids.