A versatile enzyme from Bacillus opens greener path to water-soluble nutraceuticals

Sadie Harley
scientific editor

Robert Egan
associate editor

Researchers at National Taiwan University have discovered a versatile enzyme from Bacillus subtilis that efficiently attaches phosphate groups to a wide variety of phenolic molecules, offering a sustainable and precise alternative to conventional chemical phosphorylation methods. This breakthrough offers a greener way to boost drug solubility and develop more effective nutraceuticals and prodrugs.
The study is in ACS Catalysis.
Many natural compounds, such as flavonoids, stilbenoids, and curcuminoids, show promising biological activities but are poorly soluble in water. This limits their absorption in the body. One proven way to overcome this barrier is by adding a phosphate group, which greatly improves solubility and bioavailability. However, current chemical approaches are complex and often lack precision.
The research team, led by Prof. Nan-Wei Su, identified a new enzyme called phenolic phosphate synthetase (BsPPS). Remarkably, this single enzyme was able to phosphorylate more than 30 different natural compounds, including flavonoids, chalcones, stilbenoids, anthraquinones, coumarins, coumestans, and curcuminoids, with high conversion rates for many of them.
"This is the first time we've seen one phosphorylation enzyme capable of handling such a diverse range of natural phenolic structures," says corresponding author Prof. Su. "It suggests that bacteria may use this strategy to metabolize phenolic compounds in their environment."
How it works and why it matters
The researchers also revealed how BsPPS works: in a two-step relay, the enzyme grabs a pyrophosphate from ATP, briefly holds it on a histidine site, lets one phosphate go, and then passes the other to the phenolic compound. Bioinformatic analyses show that BsPPS belongs to a previously unexplored family of enzymes widely distributed in bacterial genomes, suggesting that many similar biocatalysts remain to be discovered.
By providing a biocatalytic route to make soluble polyphenol derivatives, BsPPS could simplify the development of phosphate prodrugs and help design the next generation of nutraceuticals.
"Using these enzymes, we can envision a greener, more selective way to create medicines and supplements that work better in the body," says Prof. Su.
More information: Chen Hsu et al, Molecular Insights into a Promiscuous Dikinase Catalyzing Monophosphorylation of Structurally Diverse Natural Polyphenols, ACS Catalysis (2025).
Journal information: ACS Catalysis
Provided by National Taiwan University