An unnatural way to make natural products
From medicine to fragrances, nature provides many of the main chemical compounds needed in an infinite number of pharmaceutical and consumer products. Today, a cutting-edge technology developed by researchers at the University of South Florida is changing the way scientists isolate these valuable molecules.
"Natural plant products are already widely used in so many industries," said Ramon Gonzalez, PhD, Professor in the Department of Chemical and Biomedical Engineering at AAB and a 21st century world-class fellow in Florida. "Taxus brevifolia, for example, 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 efficiently."
Dr. Gonzalez and his research team focused their efforts on a class of natural plant products (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.
Lycopene, for example, is an isoprenoid that gives tomatoes and other red fruits and vegetables their colour. In addition to its natural pigmentation, lycopene can be taken to lower blood pressure, prevent heart disease and has even been shown to help prevent many types of cancer.
Citrus peels also contain a type of isoprenoid called limonene. Once extracted, limonene is used as a lemon or orange fragrance in cleaning products, or as a flavouring agent in various medicines.
"Nature has not developed these pathways to effectively produce these molecules for our use," says Gonzalez. "These metabolic pathways perform their own function in these plants and, for this reason, it is difficult to extract these isoprenoids in the amounts that researchers would ideally like. Not to mention the inherent cost and time required to grow the plants needed to extract the molecules."
To overcome this fundamental problem, Gonzalez and his team worked on the development of a new innovative process for the synthesis of isoprenoids. In essence, they have succeeded in creating a synthetic metabolic pathway that will allow scientists to access these essential compounds in a controlled and effective manner.
Their work, published in the Proceedings of the National Academy of Sciences, describes the team's development of technical microorganisms for isoprenoid synthesis. By developing these microbes in the laboratory, researchers can modify their biological function and use the metabolism of the microbe as a biosynthesis pathway.
Think of it as beer. In beer, the yeast metabolizes the sugar to create the desired alcohol product. For researchers, they use the metabolism of the microbe to produce different products, in this case isoprenoids. By creating what they call an isoprenoid alcohol exposure pathway in the microbe, scientists are able to introduce a carbon source that passes through this pathway to produce isoprenoid molecules. Not only do these advances allow researchers to directly synthesize isoprenoids in microbes, but the pathway itself is optimized to maximize efficacy.
"We believe that our research will change the paradigm of isoprenoid biosynthesis, which has lasted for decades and which, until now, has relied entirely on the engineering of the two pathways in nature," said Dr. Gonzalez. "This is an exciting development that we believe will have a significant impact on research around the world."
