Discovery of a novel phosphotransferase from Bacillus subtilis that phosphorylates a broad spectrum of flavonoids

Flavonoids are associated with health benefits, but most of them have poor oral bioavailability due to their extremely low aqueous solubility. Flavonoid O-phosphorylation suggests a potent modification to solve the problems. Here, we isolated, identified and characterized an unprecedented phosphotransferase, flavonoid phosphate synthetase (BsFPS), from B. subtilis. The enzyme catalyzes the ATP-dependent phosphorylation of flavonoid to generate flavonoid monophosphates, AMP and orthophosphate. BsFPS is a promiscuous phospho-transferase that efficiently catalyzes structurally-diverse flavonoids, including isoflavones, flavones, flavonols, flavanones and flavonolignans. Based on MS and NMR analysis, the phosphorylation mainly occurs on the hy-droxyl group at C-7 of A-ring or C-4 ' of B-ring in flavonoid skeleton. Notably, BsFPS is regioselective for the ortho-3 ',4 '-dihydroxy moiety of catechol-containing structures, such as luteolin and quercetin, to produce phosphate conjugates at C-4 ' or C-3 ' of B-ring. Our findings highlight the potential for developing biosynthetic platform to obtain new phosphorylated flavonoids for pharmaceutical and nutraceutical applications.

Automated summary

Flavonoid O-phosphorylation provides a potent modification to enhance the oral bioavailability of flavonoids. The enzyme BsFPS, discovered in this study, efficiently catalyzes the phosphorylation of structurally-diverse flavonoids. The findings highlight the potential for developing biosynthetic platforms to obtain new phosphorylated flavonoids for pharmaceutical and nutraceutical applications.