Genetically engineered E. coli may improve drug development

As part of the process of producing natural benzoxazole, graduate student Huanrong Ouyang selects a single colony of E. coli from a plate and inoculates it into a liquid culture. Credit: Texas A & M Engineering

Whether you are taking muscle relaxants or heart medications, you may be using medications that contain synthetically produced benzoxazoles. Natural benzoxazoles show more important potential in medicine, but the time to develop organic and inherently undesired properties hinders their use.

Dr. Xuejun Zhu, an assistant professor at Artie McFerrin’s Faculty of Chemical Engineering at Texas A & M University, along with graduate student Huanrong Ouyang and two undergraduate students Joshua Hong and Jeshua Malroy. We use coli to synthesize natural benzoxazole. An efficient, environmentally friendly and cost-effective way to produce them for future drug development.

Their work was published in the journal of the American Chemical Society ACS Synthetic Biology 2021.

Benzoxazole is a heterocyclic compound composed of carbon, hydrogen, oxygen and nitrogen. It can be produced synthetically, but it is also found in bioactive natural products such as nataxazole, caboxamycin and calciummycin. Synthetic benzoxazoles are found in synthetic medicines ranging from chlorzoxazone (a muscle relaxant) to tafamidis (for the treatment of heart disease).

However, natural benzoxazoles are rarely used due to their undesired properties such as the time it takes to organically produce the compound, its high toxicity, its low potency, and its low solubility. Research on natural benzoxazoles is limited, but it contains many qualities that show potential future use in the treatment of cancer, anthelmintic and antibacterial agents. For example, some natural benzoxazoles exhibit promising cytotoxic activity to combat a variety of tumor cell lines.

“Currently, the natural method for producing the compound benzoxazole is very slow, sometimes taking a week or more,” Zhu said. “Natural compounds can also cause excessive levels of toxicity or other unwanted properties that limit their use.”

Researchers turned to Escherichia coli, a bacterium found in the environment and in the intestines of humans and animals, hoping to extract and fight certain qualities of natural benzoxazole.

“Compared to other microorganisms, E. coli grows very fast,” Ouyang said. “Modern researchers have done a lot of research on E. coli, especially for large-scale production, which simplifies genetic engineering to improve productivity.”

Researchers have modified E. coli with several essential genes to make natural benzoxazole. Binding of engineered E. coli with precursor-oriented biosynthesis develops pathways to produce natural benzoxazoles at a faster rate.

“Our research shows that we can produce three types of benzoxazoles at the same time,” says Zhu. “Each type can have different biological activities such as antibacterial, antiparasitic, anticancer, etc.”

By adjusting variables, such as the use of different precursors, researchers have further expanded the structural diversity of benzoxazoles, which are unique to natural benzoxazoles to improve solubility and efficacy while reducing toxicity levels. You can reverse some of the problems with.

“We have found that our E. coli-based platform can recognize selected precursors such as fluorine and chlorine and incorporate them into scaffolds,” says Ouyang. “Our research serves as the foundation for future drug discovery and development.”

Sustainable methods of developing natural benzoxazoles have the potential to be used in a variety of medicines with many advantages over synthetically produced benzoxazoles. Researchers hope this is a step towards an easy and cost-effective way to generate novel benzoxazole analogs through protein engineering and combinatorial biosynthesis.

This work is supported by the Texas A & M Engineering Experiment Station and startup funding from the Chemical Engineering Department.

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For more information:
Huanrong Ouyang et al, E. The coli-based biosynthetic platform expands the structural diversity of natural benzoxazoles. ACS Synthetic Biology (2021). DOI: 10.1021 / acssynbio.1c00228

Quote: Genetically engineered E. coli was obtained from https: // on January 14, 2022 for drug development (January 14, 2022). May improve

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Genetically engineered E. coli may improve drug development

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