Rice University chemist Han Xiao and his team successfully extended the genetic code of the bacterium Escherichia coli to create a synthetic building block, a “non-cone amino acid”. The result is a survival index for oxidative stress.
This work, they say, is a step towards technology that allows the creation of new proteins and organisms with many useful functions.
Their research appeared in the journal Cell Press Chem.
Amino acids are the building blocks of DNA. In general, organisms only need 20 of them to program all the proteins necessary for life. But Xiao, with the help of a $ 1.8 million grant from the National Institutes of Health, figured out how a 21st amino acid would enable the design of “unnatural organisms”. specific purposes.
The new study does that by engineering bacteria that produce an additional amino acid, called 5-hydroxyl-tryptophan (5HTP), that occurs naturally in humans as a precursor to the neurotransmitter serotonin, but not in E. coli. The new production process of 5HTP prompts the bacteria to produce a protein that fluorescence when the organism is under metabolic stress.
“This process requires a lot of interdisciplinary techniques,” said Xiao. “In this study, we combined chemical synthesis, synthetic biology, and metabolic engineering to create a synthetic strain and encode the 21st amino acid, and then use it to make protein.” desire.”
Xiao says programming the unnatural bacteria is a three-step process: First, the researchers led by graduate student Yuda Chen created a bio-transcription machine for the amino acid, 5HTP. Second, they find and target an empty codon – a sequence in DNA or RNA that doesn’t make a protein – and genetically modify it to encode 5HTP. Third, by grafting enzyme clusters from other species into E. coli, they gave the bacteria the ability to produce 5HTP.
“These 5HTP-containing proteins, isolated from programmed bacteria, can be labeled with drugs or other molecules,” Xiao said. “Here, we show that the strain itself can act as a vital indicator for reactive oxygen species and that the limit of detection is really low.”
Although researchers have reported the creation of more than 200 non-amino acids to date, most of them cannot be synthesized by their host organisms. “This has been a continuous field for decades, but before that people focused on the chemistry part,” Xiao said. “Our vision is to create whole cells with 21st amino acids that allow us to investigate biological or medical problems in vivo, rather than just processing the cells in the lab.
“Moving this technology to host species eliminates the need to put artificial building blocks in an organism, as they can synthesize and use it,” he said. “That allows us to study non-conical amino acids at a higher, whole-organism level.”
Ultimately, the researchers hope for custom building blocks that will allow target cells, like those in a tumor, to create their own therapeutic drugs. “It’s an important future direction for my lab,” said Xiao. “We want cells to detect diseases, make better drugs and release them in real time. We don’t think that’s too far-fetched.”
Co-authors of the paper are postdoctoral students Rice Juan Tang, Lushun Wang and Zeru Tian, college student Adam Cardenas and visiting scholar Xinlei Fang, and Abhishek Chatterjee, an assistant professor of chemistry. study at Boston College. Xiao is Young Investigator Norman Hackerman-Welch and Assistant Professor of Chemistry.
The scientists direct the bacteria with the extended genetic code to develop extremely high heat resistance
Yuda Chen et al., Generates bacterial cell with 5-Hydroxytryptophan as the 21st amino acid building block, Chem (Year 2020). DOI: 10.1016 / j.chempr.2020.07.013
Provided by Rice University
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