Chemists enlarge genetic code of E. coli to make 21st amino acid

Posted On December 11, 2020     

The chemist Han Xiao and his team at Rice University have successfully extended the Escherichia coli bacteria's genetic code to create a synthetic building block, a noncanonical amino acid. The product is a living indicator for oxidative stress.
As per the researchers, the work is a step toward technologies that will let the generation of novel proteins and organisms with an array of useful functions.

Amino acids refer to the building blocks of DNA. In general, organisms require only 20 of them to program the complete set of proteins essential for life. But this research set out to see how a 21st amino acid would enable the design of "unnatural organisms" that serve specific purposes.

The new study does just that by engineering bacteria to make the extra amino acid, called 5-hydroxyl-tryptophan (5HTP), which comes naturally in humans as a pioneer to the neurotransmitter serotonin, but not in E. coli. The novel production of 5HTP triggers the bacteria to create a protein that fluoresces when the creature is under metabolic stress.

The process needs a lot of interdisciplinary techniques. In the study, the scientist joined synthetic biology, synthetic chemistry, and metabolic engineering to produce a strain that encodes and synthesizes a 21st noncanonical amino acid and then utilize it to create the desired protein.
The process of programming autonomous unnatural bacteria comprise of three-step. First, bioorthogonal translational machinery for the amino acid 5HTP is created. Second, they found and targeted a blank codon, which is a sequence in DNA or RNA that doesn't manufacture a protein—and genetically modified it to encode 5HTP. Third, by grafting the enzyme clusters from other species into E. coli, they gave the bacteria the skill to produce 5HTP.

The researchers have reported the formation of more than 200 noncanonical amino acids so far. But many of them could not be synthesized through their host organisms. Though previously, people focused on the chemical part in this study, the scientist's vision is to engineer whole cells with the 21st amino acid to investigate medical or biological problems in living organisms.

By moving this technology to the host, species reduce the desire to inject artificial building blocks into an organism, as they can produce and use it independently. This allows us to study noncanonical amino acids at a larger or whole organism level.

Eventually, the researchers hope modified building blocks will permit targeted cells, similar to those in tumors, to create their own therapeutic drugs. The ongoing research initiative is positively influencing the natural and unnatural amino acids market at the global level. These are creating a beneficial opportunity for the key players working in the amino acid industry.

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