Texas Tech University

Texas Tech Researcher Discovers Genes to Create Tropane Alkaloids

January 30, 2019 | By: Karen Michael 

Professor Collaborated with Michigan State Researchers to Allow Growth of Pharmaceuticals in Space

Space explorers couldn't possibly pack all of the medicine they might need for a long trip, but a Texas Tech University researcher is part of an effort to make it easier to grow necessary drugs in space.

John D'Auria, an assistant professor of chemistry and biochemistry at Texas Tech, is working with Michigan State University researchers to discover the genes and enzymes that plants use to create tropane alkaloids, or chemicals made by plants that are used in many medicines.

D'Auria worked with MSU researchers Cornelius S. Barry, A. Daniel Jones and Matthew A. Bedewitz to identify two genes in Atropa belladonna, or deadly nightshade. These genes code two enzymes to make tropinone in plants.

The researchers also engineered the enzymes into tobacco plants, which don't normally make tropane alkaloids. The modified plants then were able to produce tropinone, the most simple tropane alkaloid.

This research is important, D'Auria said, because it could be used for synthetic biology. Scientists could make tropane alkaloids in organisms that do not usually make them, such as bacteria, yeast and other plants.

"Compounds like this are great candidates for engineering them in yeast or bacteria because we can then use them as substitutes for classical organic synthesis for the prospects of space exploration. There are no petrochemicals in space," D'Auria said. "That means if we want to make complex organic molecules, we will need to use bacteria, yeasts and plants to make them for us. This is the ultimate goal of our grant, and the paper is a major step on that road."

Even for a trip to Mars, D'Auria said, explorers would need years. They couldn't possibly take all of the medicine and food they would need for a longer journey to colonize a planet. If scientists can figure out how to make the pharmaceuticals in yeast or bacteria, or by engineering a food plant like tomatoes to grow a drug within its non-edible roots, they could make necessary medicines in space instead of taking medicine with them.

Currently, D'Auria said many medicines are made in test tubes from compounds coming from the Earth via the petroleum industry. Petrochemicals will not be available in space, he said, so the ability to grow by other means is important.

Researchers on the project also hope that having a new way to produce tropane alkaloids could help with the production of medicinal compounds right here on Earth, D'Auria said.

D'Auria said he feels that he and his fellow researchers have made a great leap in understanding a class of plant-derived chemicals that are critical for human health. Tropinone was first chemically synthesized in 1901, but the enzymes that plants use to make it were unknown until this research was completed and an article was published in Nature Communications in December.

Two tropane alkaloids known as atropine and scopolamine are listed on the World Health Organization's essential list of modern pharmaceuticals, D'Auria said.

"The atropine and scopolamine are really important medicines," he said. "What they do is really important for a lot of human health."

Atropine is the chemical used to dilate the pupils by eye doctors, while scopolamine is used both for motion sickness and to treat nausea among chemotherapy patients. Understanding how these compounds are made biochemically could help to produce them in bacteria and yeast, and to aid in the design of new variants for medicinal use.

He and his students – both graduate and undergraduates – are embarking on a set of projects that will wind up with major breakthroughs in metabolic engineering and synthetic biology, D'Auria said. He currently has four doctoral students working on the project, which is about halfway through a three-year grant.

"I am proud that work done at TTU made it to one of the most premier scientific journals in the world. I fully intend to train TTU students to continue with the quality and passion for this subject that I have had here for the past five years," D'Auria said.

The Texas Tech researcher said others at the university assisted with the work, including Guigen Li and Michael Findlater and their respective labs.

The researchers have a grant of $800,000 from the National Science Foundation. Texas Tech's share of that grant funding is $332,348.

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