Efficient Biosynthesis of 8-Prenylkaempferol from Kaempferol by Using Flavonoid 8-Dimethylallyltransferase Derived from <i>Epimedium koreanum</i>

The genus <i>Epimedium</i> includes popular Chinese medicinal plants, and icariin and its precursor icaritin are the key bioactive components of <i>Epimedium</i>. Here, we identified flavonoid 8-dimethylallyltransferase (F8DT) in the authentic medicinal material of <i>Epimedium koreanum</i>, which is a key gene in the icariin biosynthesis pathway. This enzyme can catalyze the synthesis of 8-prenylkaempferol (8PK) from kaempferol. The catalytic ability of the rate-limiting enzyme <i>Ek</i>F8DT was significantly improved by truncating its N-terminal intrinsically disordered regions (IDRs) and enhancing the flux of the mevalonate pathway. Icaritin was also successfully synthesized by introducing flavonoid 4'-<i>O</i>-methyltransferase into the <i>Saccharomyces cerevisiae</i> strain. Finally, the highest production of 8PK and icaritin (3.6 g/L and 172.0 mg/L, respectively) was obtained in the <i>S. cerevisiae</i> strain.