An artificial way to make natural products

From medicine to perfume, nature provides many of the essential chemical compounds needed for an infinite number of pharmaceuticals and consumer products. Today, state-of-the-art technology developed by researchers at the University of South Florida is changing the way scientists isolate these valuable molecules.

"Herbal natural products are already widely used in many industries," said Ramon Gonzalez, Ph.D., professor in the USF Chemical and Biomedical Engineering Department and 21st Century World Class Fellow. in Florida. "Taxus brevifolia, for example, the Pacific yew, contains molecules that are used to produce a chemotherapy drug for several cancer treatments.The problem is that many of these products are expensive and difficult to extract effectively."

Gonzalez and his research team focused their efforts on a class of natural products of plant origin (PNP) called isoprenoids. With more than 50,000 of these isoprenoids synthesized in nature, they represent one of the most structurally and chemically diverse classes of molecules known to man.

Lycopene, for example, is an isoprenoid that gives color to tomatoes and other red fruits and vegetables. In addition to its natural pigmentation, lycopene can be used to lower blood pressure, prevent heart disease and has even been shown to help prevent several types of cancer.

Citrus peels also contain a type of isoprenoid called limonene. When extracted, limonene is used as a lemon or orange scent in cleaning products or as a flavoring agent in different medicines.

"Nature has not developed these pathways to efficiently produce these molecules for our use," Gonzalez said. "These metabolic pathways have their own function in these plants, and so it is difficult to extract these isoprenoids in the amounts that researchers would ideally like, not to mention the cost and time involved in growing the plants needed to extract them. molecules of. "

To overcome this fundamental problem, Gonzalez and his team have developed a new, innovative process for isoprenoid synthesis. Essentially, they have been able to create a synthetic metabolic pathway that will allow scientists to access these essential compounds in a controlled and efficient manner.

Their work, published in Proceedings of the National Academy of Sciences, describes the development by the team of microorganisms designed for the synthesis of isoprenoids. By developing these microbes in the laboratory, researchers can modify their biological function and use the metabolism of the microbe as a biosynthetic pathway.

Think of it as beer. In beer, the yeast metabolizes the sugar to create the desired product: alcohol. For researchers, they exploit the metabolism of the microbe to produce different products, in this case isoprenoids. By creating what is called an isoprenoidal alcohol pathway within the microbe, scientists are able to introduce a carbon source that goes through the pathway to produce molecules of the same kind. isoprenoid. The benefits are twofold. not only do these advances allow researchers to directly synthesize isoprenoids in microbes, but the pathway itself is optimized to optimize its effectiveness.

"We are confident that our research will change the paradigm of isoprenoid biosynthesis, which has been up to several decades, which until now was entirely based on the engineering of the two existing pathways in nature." said Gonzalez. "We believe that this breakthrough will have a significant impact on research conducted around the world."