Rice University chemist Han Xiao and his team have successfully extended the genetic code of Escherichia coli bacteria to produce a synthetic building block, a “non-canonical amino acid.”; The result is a vivid indicator of oxidative stress.
The work, they say, is a step towards technologies that will allow the generation of proteins and new organisms with a variety of useful functions.
Their study appears in the journal Cell Press Chem.
Amino acids are the building blocks of DNA. In general, organisms need only 20 of them to program the entire set of proteins needed for life. But Xiao, with the help of a $ 1.8 million grant from the National Institutes of Health, determined how a 21st amino acid would enable the design of “unnatural organisms” that serve specific purposes.
The new study does exactly that from bacterial engineering to produce the extra amino acid, called 5-hydroxyl-tryptophan (5HTP), which occurs naturally in humans as a precursor to the neurotransmitter serotonin, but not in E. coli. New production of 5HTP causes bacteria to produce a protein that fluoresces when the body is under metabolic stress.
“The process requires a lot of interdisciplinary techniques,” Xiao said. “In this study, we combined synthetic chemistry, synthetic biology, and metabolic engineering to create a strain that synthesizes and encodes a non-canonical 21st amino acid, and then uses it to produce the desired protein.”
Xiao said programming natural autonomic bacteria was a three-step process: First, researchers led by graduate student Yuda Chen created the bioortogonal translation machine for the amino acid, 5HTP. Second, they found and targeted a blank codon – a sequence in DNA or RNA that does not produce a protein – and genetically edited it to encode 5HTP. Third, by grafting enzyme clusters from other species in E. coli, they gave the bacteria the ability to produce 5HTP.
“These 5HTP-containing proteins, isolated from programmed bacteria, can be further labeled with drugs or other molecules,” Xiao said. “Here, we show that the strain itself can serve as a living indicator for reactive oxygen species, and the detection limit is really low.”
While researchers have reported the creation of more than 200 non-canonical amino acids to date, most of them cannot be synthesized by their host organisms. “This has been a constant field for decades, but before that people were focused on the chemical part,” Xiao said. “Our vision is to engineer whole cells with the 21st amino acid that will allow us to investigate biological or medical problems in living organisms, rather than just dealing with cells in the laboratory.
“The transfer of this technology to the host species eliminates the need to inject artificial building blocks into an organism because they can synthesize and use it themselves,” he said. “It allows us to study non-canonical amino acids at a higher level, the whole organism.”
After all, researchers hope that blocks of personalized buildings will allow target cells, such as those with tumors, to make their own therapeutic drugs. “This is an important direction in the future for my lab,” Xiao said. “We want cells to detect disease, make better medicines and release them in real time. We don’t think it’s too far away.”
The co-authors of the paper are Rice Juan Tang’s descendants, Lushun Wang and Zeru Tian, university student Adam Cardenas and visiting scholar Xinlei Fang, and Abhishek Chatterjee, an assistant professor of chemistry at Boston College. Xiao is Young Investigator Norman Hackerman-Welch and an assistant professor of chemistry.
Scientists direct bacteria with extended genetic code to evolve extreme heat tolerance
Yuda Chen et al, Creation of bacterial cells with 5-hydroxyrryptophan as a 21st block building block of amino acids, Chem (2020). DOI: 10.1016 / j.chempr.2020.07.013
Provided by Rice University
citation: Chemists extend E. coli genetic code to produce 21st amino acid, giving new capabilities (2020, August 12) restored August 12, 2020 by https://phys.org/news/2020-08-chemists -genetic-code- coli-21st.html
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