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An unnatural way to make natural products

  An unnatural way to produce natural products
James Clomburg, a researcher at the University of South Florida, is harvesting microorganisms from an agar plate. Credit: University of South Florida

From medicine to perfumes, nature provides many of the most important chemical compounds needed in an infinite number of pharmaceuticals and consumer products. Now, a cutting edge 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 so many industries," Dr. Ramon Gonzalez, a professor at the USF Department of Chemical Engineering and Biomedical Engineering, and a world-class 21

st-century scientist in Florida. "Taxus brevifolia, such as the Pacific yew, contains molecules that are used to make a chemotherapeutic agent for various cancer treatments, but the problem is that many of these products are expensive and difficult to extract efficiently."

Gonzalez and his colleagues The research team focused its efforts on a class of plant-derived natural products (PNPs) called isoprenoids. With more than 50,000 of these naturally synthesized isoprenoids, they represent one of the most structurally and chemically diverse classes of molecules known to man.

For example, lycopene 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 even prevent some types of cancer.

Citrus peel also contains a type of isoprenoid called limonene. When extracted, limonene is used as a lemon or orange fragrance in detergents or as a flavoring in various medications.

  An unnatural way to produce natural products
Researcher James Clomburg shows an agar plate containing a strain of E. coli K-12 prepared for isoprenoid production. Credit: University of South Florida

"Nature has not developed these ways to efficiently produce these molecules for our use," said Gonzalez. "These metabolic pathways perform their own functions in these plants, which is why it is difficult to extract these isoprenoids in the amounts that the researchers would most like, not to mention the cost and time required to cultivate the plants are from which the molecules are extracted. " "

To solve this fundamental problem, Gonzalez and his team have developed an innovative new method for the synthesis of isoprenoids, in essence, they have succeeded in creating a synthetic pathway through which scientists control and efficiently access these essential compounds

Their work has been published in the Proceedings of the National Academy of Sciences ] describing the development of technical microorganisms for the synthesis of isoprenoids by the team.Through the development of these microbes in a laboratory, researchers can study their biological Change function and use the microbial metabolism as a pathway for biosynthesis.

Imagine you were brewing beer In yeast, yeast metabolizes sugar to produce the desired product – alcohol For researchers, they use the metabolism of microbes to produce various products – in the sem case isoprenoids. By developing a so-called isoprenoid alcohol pathway within the microbe, scientists can introduce a carbon source that passes the path to produce isoprenoid molecules. The benefits are twofold; These advances not only allow researchers to directly synthesize isoprenoids in microbes, but the pathway itself is optimized to maximize efficiency.

"We believe that our research will change the decade-long paradigm of isoprenoid biosynthesis that has been fully established so far. I have relied on constructing the two existing natural pathways," said Gonzalez. "It is an exciting advance that we believe will have far-reaching impact on research around the world."

Researchers create "shortcuts" to terpene biosynthesis in E. coli

Further information:
The Isoprenoid Alcohol Pathway, a Synthesis Pathway for Isoprenoid Biosynthesis, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073 / pnas.1821004116, https://www.pnas.org/content/early/2019/06/10/1821004116

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University of South Florida

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An unnatural way to make natural products (2019, 11 June)
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