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.