July 28, 1999
La Jolla, CA – The three-dimensional structure of a linchpin enzyme plants need to thrive – and one viewed as a key player in the growing nutraceutical market – has been revealed in atomic detail by scientists at The Salk Institute.
The enzyme, called chalcone synthase, is the first in a class of commercially promising enzymes – the polyketide synthases – to have its structure deciphered. This work is expected to lead to “designer enzymes” that one day may churn out made-to-order dietary supplements and health products.
“From a commercial standpoint, it’s interesting to note that many polyketide synthases make compounds that not only enhance plant growth, development and disease resistance, but are also beneficial for people,” said Salk Associate Professor Joseph P. Noel, senior author of the study, which appears in the current issue of Nature Structural Biology.
For example, anthocyanin – a pigment made from a polyketide synthase that gives flowers their color and protects plants from ultraviolet light – is a popular nutritional supplement with antioxidant properties. Studies suggest that antioxidants may have anti-aging and anti-carcinogenic effects.
Resveratrol, the substance in red wine thought to be one of the keys to the cholesterol-lowering effects of the Mediterranean diet, is made by an enzyme very similar to chalcone synthase. This health benefit is a lucky accident – grapes produce resveratrol to protect themselves from fungal invasion.
“Presumably,” said Noel, “if we can understand both what these molecules do in the human body and how plants make them, we can devise novel compounds that might be even better nutraceuticals and more healthful dietary supplements.
“And, by studying what they do in plants, we should also be able to engineer hardier crops, ones more resistant to pests and other assaults.”
Using X-ray crystallography techniques, Noel and his colleagues solved the structure of the chalcone synthase found in alfalfa. It appears that all chalcone synthases are closely related, however, so the group believes that their studies will supply knowledge of enzyme mechanisms that will apply to most members of the group.
“The structural study demonstrates how chalcone synthase uses its active site to carry out a complex series of reactions,” said Noel. “It should be possible to combine this information with the bank of plant genome sequence data to identify polyketide synthases with new substrate and product specificity, as well as to engineer completely novel enzymes. Both approaches should yield molecules with commercial potential.”
First author of the study is Jean-Luc Ferrer, a visiting scientist from Centre National de la Recherche Scientifique in Grenoble, France. Salk co-authors include Joseph M. Jez, recipient of a fellowship from the Maximillian E. and Marion O. Hoffman Foundation, and research assistant Marianne E. Bowman. The study was completed in collaboration with Richard A. Dixon at the Samuel Roberts Noble Foundation in Ardmore, Okla. The study, titled “Structure of Chalcone Synthase and the Molecular Basis of Plant Polyketide Biosynthesis” was supported by the National Institutes of Health.
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.