Making Natural Products in an Unnatural Way

Nature provides various crucial chemical compounds needed in an endless number of pharmaceuticals and consumer products, from medicine to fragrances. Now, researchers at the University of South Florida have engineered a cutting-edge technique that is changing the way scientists isolate these precious molecules. The team published the work in the Proceedings of the National Academy of Sciences.

Professor in the USF Department of Chemical and Biomedical Engineering and a Florida 21st Century World Class Scholar, Ramon Gonzale, Ph.D., said that natural plant products are already widely used across so many industries. For instance, Taxus brevifolia, the Pacific yew plant, 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 challenging to extract efficiently.

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

For example, lycopene is an isoprenoid that gives tomatoes and other red fruits and vegetable their colors. Aside from its natural pigmentation, lycopene can be taken to lower blood pressure, prevent heart disease, and has even been shown to help prevent several types of cancer.

Also, citrus fruit peels contain a type of isoprenoid called limonene. When extracted, limonene is used as the lemon or orange fragrance in cleaning products, or as a flavoring agent in different medications.

Gonzale noted that nature didn't develop these pathways to produce these molecules for our use efficiently. These metabolic pathways serve their function in these plants, and because of that, it's challenging to extract these isoprenoids in the amounts researchers would ideally prefer. Not to mention the inherent cost and time required to cultivate the plants needed from which to obtain the molecules.

To overcome this fundamental problem, Gonzale and his team worked to develop a new process for synthesizing isoprenoids. Primarily, the team has been able to create a synthetic metabolic pathway that will allow scientists to access these essential compounds in a controlled and efficient way.

The research outlines the group's development of engineered microorganisms for synthesizing isoprenoids. The researchers developed these microbes in a lab and can modify their biological function and use the microbes' metabolism as a pathway for biosynthesis.

Gonzale concluded that they believe their research will change the decades-long paradigm for isoprenoid biosynthesis, which will now have entirely relied on engineering the two pathways existing in nature. It is an exciting advancement that the team feel will have broad-ranging impacts on research happening around the world.

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