Research funded by the National Science Foundation (NSF) and the Salk Institute in San Diego, California, have succeeded in converting chalcone synthase, a biosynthetic protein enzyme found in all higher plants, into an efficient resveratrol synthase.
Grapes produce resveratrol - found in red wine - to defend against fungal invasion. Researchers at the Salk Institute have succeeded in deciphering the three-dimensional structure of the plant enzyme that creates this molecule.
Furthermore, they have worked out the crucial differences between common plant enzymes known as chalcone synthases and their resveratrol-producing relatives, the much rarer stilbene synthases.
Scientists realised decades ago that chalcones and stilbenes, two important classes of plant products, were produced by closely related enzymatic proteins. Chalcone-derived natural chemicals fulfill a number of important biological functions in plants, including roles in plant fertility, disease resistance and flower color. However, production of resveratrol and other rare anti-fungal stilbenes occurs in just a few plant species, including grapevines, peanuts, blueberries and some pine trees.
Using the tools of structural biology, Michael Austin, a graduate student at the Salk Institute and the University of California solved the three dimensional structure of resveratrol synthase and compared its shape to its relative chalcone synthase - uncovering the differences between these related plant enzymes.
Austin - part of a research team led by biochemist Joseph Noel from the Salk Institute - and colleagues used this knowledge to convert a chalcone synthase from alfalfa into an efficient resveratrol-producing factory, simply by changing a few amino acids.
"This biotechnological advance will allow us to 'engineer' natural resveratrol production into crop plants via a small modification of that plant's own chalcone synthase gene, as occurs naturally in grapes and a few other plants," said Noel.
The research results appear in the September issue of the journal Chemistry & Biology.
Resveratrol is thought to contribute to the improved cardiovascular effects associated with moderate consumption of red wine. And laboratory studies have demonstrated an impressive list of its further health benefits, including roles as anti-oxidants, cancer preventing agents, blood thinners and blood pressure-lowering compounds.
Resveratrol may even extend lifespan, reported American scientists in July, after they discovered that the red wine compound had the same effect on fruit flies and worms as the use of caloric restriction, one of the few methods demonstrated in several studies to retard ageing and promote lifespan among animals.
The findings appear to suggest that people could take a pill to achieve the same benefits as strict dieting to live longer. However while supplement makers are already beginning to market the antioxidant resveratrol in capsules, to allow consumers to gain the health benefits of the compound without the alcohol, the new research has not yet been tested on people.
Resveratrol is also difficult to formulate for supplements as it oxidises very quickly, losing its efficacy.
Writing in an early online edition of Nature (14 July 2004; doi:10.1038/nature02789), David Sinclair from Harvard Medical School and colleagues at the University of Connecticut and Brown University in Rhode Island reported that resveratrol activated proteins called sirtuins in fruitflies and worms, extending their lifespan without reducing fertility.