Biosynthesis of stilbenes and flavonoids in sorghum and stilbene profiles of Colletotrichum sublineola-infected sorghum mesocotyls. Image: Lo et al, Nature Communications

Enzyme unlocks potential for health-promoting compounds

28 July 2023

A HKU team in collaboration with researchers in Australia, mainland China and Japan show that sorghum and wild sugarcane could be used to produce O-methylated stilbenes with potential uses in the food and pharmaceutical sectors.

Stilbenes are natural compounds found in various plants that have shown potential health benefits for humans, with a unique chemical structure consisting of two aromatic rings linked by a double bond. While resveratrol, found in grapes and red wine, is the most well-known stilbene, there has been increasing interest in other types of stilbenes that could offer additional health benefits.

O-methylated stilbenes which are produced by introduction of a methyl group (-CH3) to a hydroxyl (-OH) group on the stilbene backbone are promising compounds for research. Some plant species, such as sorghum and wild sugarcane, have been found to produce O-methylated stilbenes in response to abiotic or biotic stress and may have greater potency and bioavailability than non-methylated stilbenes. The biosynthesis of O-methylated stilbenes has potential applications in the production of dietary supplements and pharmaceuticals.

A research team led by Dr Clive Lo from the School of Biological Sciences at the University of Hong Kong collaborated with the University of Queensland, Australia and scientists in Mainland China and Japan, have found a novel enzyme which appears to be responsible for catalysing the production of O-methylated stilbenes. The discovery suggests a new way to produce O-methylated stilbenes in larger quantities and at lower costs. The research findings were published in Nature Communications.

Stilbenes are specialised metabolites sporadically distributed across the plant kingdom which are thought to  maintain reactive oxygen species homeostasis and protect against microbial attacks. Their anti-aging, anti-neurodegeneration, anti-diabetes, and chemo-prevention properties are of interest in nutritional and pharmaceutical research. Over 200 clinical trials have been launched to explore the potential health benefits of stilbenes like resveratrol and pterostilbene which are now commercialised as dietary supplements.

Lo and his colleagues showed how sorghum and wild sugarcane could produce different types of O-methylated stilbenes, such as pinostilbene, pterostilbene and isorhapontigenin. They used advanced genetic techniques to identify the key enzyme that mediates the specific chemical modification of stilbene in sorghum. This modification affects the biological activity of the stilbene, including its antioxidant and anti-inflammatory properties. They named the enzyme SbSOMT,

The team found that SbSOMT is unique to sorghum plants and originated from a group of related proteins called caffeic acid O-methyltransferases (COMTs) commonly found in all other grasses. The team then presented the first crystal structure for SbSOMT.

SbSOMT uses a chemical reaction similar to COMTs in the grass family but binds to the stilbene molecule differently. This different binding mode allows SbSOMT to modify the stilbene molecule in a specific way that produces different types of O-methylated stilbenes in sorghum. These different types of stilbenes are characterized by the location of the O-methyl group on the stilbene molecule either on the A-ring or the B-ring.

In sorghum, SbSOMT modifies stilbenes in a way that produces A-ring O-methylated stilbenes, such as pinostilbene and pterostilbene. Meanwhile, wild sugarcane uses a common COMT enzyme to modify stilbenes to produce B-ring O-methylated stilbenes, such as isorhapontigenin. The difference between the A-ring and B-ring O-methylated stilbenes is due to the specific way that SbSOMT interacts with the stilbene molecule, which involves the hydrophobic Ile144 and Phe337 residues in the SbSOMT enzyme.