Enzymatic Synthesis of Thaxtomin Analogs for Agricultural and Medical Applications

Sarah Hylton

Authors:  Sarah Hylton, Guangde Jiang, Yi Zhang, Magan M. Powell, Peilan Zhang, Rosemary Loria, Yousong Ding

Faculty Mentor:   Yousong Ding

College:  College of Pharmacy

Abstract

Thaxtomins are a group of cyclic diketopiperazines that are virulence factors of many plant- pathogenic Streptomyces strains which cause the common scab potato disease. Thaxtomins represent an economically valuable and agriculturally important natural herbicide because of their ability to inhibit cellulose synthesis. It is desirable to perfect a natural synthesis route because the process is more efficient, economical, and environmentally friendly than existing chemical synthesis routes. In addition, thaxtomin analogs may represent value in the medical field due to their anti- fungal, antiviral, and antibiotic properties. Our lab developed a cell- free biocombitorial approach to synthesizing thaxtomin analogs. Biosynthesis of 124 unique thaxtomin analogs was achieved in vitro directly from simple amino acid components. This was made possible through the novel functional characterization of three biosynthetic thaxtomin enzymes: TxtA, TxtB, and TxtC. The production and functions of these enzymes was explored with the previously characterized TxtE enzyme. Furthermore, our lab demonstrated rare P450 cytochrome enzymatic activity that is capable of catalyzing both aliphatic and aromatic hydroxylation in one process. Both hydroxylation processes are valuable to biosynthesis reactions, specifically, they allowed for the production of over 40 additional novel diketopiperazine products.

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Shannon Summers
Shannon Summers (@guest_2558)
1 year ago

Hi Sarah,
Your topic is very interesting! I don’t have much of a background in pharmacy, so what would you say is the most important conclusion you made from your study?

Sarah Hylton
Sarah Hylton (@guest_3158)
Reply to  Shannon Summers
1 year ago

Hey Shannon! I’d say the most important conclusion was the variety of analogs we were able to produce. These different analogs can be now be studied individually and may be valuable medications or herbicides.

Shannon Summers
Shannon Summers (@guest_2636)
1 year ago

Hi Sarah,
Your topic is very interesting! I don’t have much of background in pharmacy, so what would you say is the most important conclusion you made from your study?

Dianela Perdomo
Dianela Perdomo (@guest_7634)
1 year ago

Hi Sarah!
Great job on your poster and presentation. Like Shannon, I don’t have an extensive background in pharmacy, but I understand the significance of having effective herbicides and being able to understand how particular substances work so that we can utilize their functions.

I’m curious as to what prompted your research. What problem or issue did your PI/yourself/your teammates identify that led you guys to study thaxtomin in particular?