Engineers create bacteria that can synthesize an unnatural amino acid

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“The nitro chemical functional group has valuable properties and has been little explored by people trying to rewire metabolism,” Kunjapur said. “pN-Phe also has a good story in the literature: You can add it to a protein in a mouse, put it back in the mice, and the immune system will no longer tolerate the original version of that protein. That ability holds promise for the treatment or preventing diseases caused by rogue proteins that the immune system struggles to block.”

Genetic code expansion methods allowed researchers to increase the “alphabet” of available amino acids encoded by DNA. By combining metabolic engineering techniques with expansion of the genetic code, the researchers were able to create a system that autonomously produces nitrated proteins.

“Because of the chemistry of the nitro functional group, the amino acid we chose as our target for this project was unconventional, and many scientists within our field may not have expected that it could be made via biosynthesis,” Kunjapur said.

The next step of this research is to optimize their methods to synthesize larger amounts of nitrated proteins and to expand this work to other microorganisms. The long-term goal is to further refine this platform for applications related to vaccines or immunotherapies, efforts that are supported by Kunjapur’s 2021 AIChE Langer Award and the National Institutes of Health Director’s New Innovator Award 2022. To further support Furthering this long-term goal, Kunjapur and Neil Butler, PhD candidate and first author of this paper, co-founded Nitro Biosciences.

“I think the implications are interesting, in that you can take a bacterium’s central metabolism, its ability to produce different compounds, and with a few modifications you can expand its chemical repertoire,” Butler said. “Nitro functionality is rare in biology and is absent from the standard 20 amino acids, but we show that bacterial metabolism is malleable enough that it can be reconfigured to create and integrate this functionality.”

Kunjapur added: “Bacteria are potentially useful drug delivery vehicles. We believe we have created a tool that could harness the ability of bacteria to produce target antigens within the body and exploit the ability of nitration to shed light on those antigens by Same time”. .”

The full list of co-authors includes Neil Butler, Sabyasachi Sen, Lucas Brown, Minwei Lin, and Aditya Kunjapur from the University of Delaware. This research was supported by a grant from the National Science Foundation (CBET 2032243).