This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Scientists have been hard at work for more than 20 years to instruct biological systems, such as E. coli cells, to produce proteins they don't naturally produce. Success could mean faster, cheaper, more innovative solutions for medicine, agriculture, materials science, environmental remediation and other industries.
The journey so far has been arduous. It seemed that the best—and possibly only—way to achieve the goal was to reprogram an organism's DNA, but that has proven fiendishly difficult and time-consuming and produces feeble results. The lab of geneticist George Church at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering at Harvard University has now devised a simpler, faster, safer and larger-scale method to make new proteins without requiring genome recoding or even any organisms.
Their tool, called AGENTEX and published in Nature, allows researchers to design proteins using up to 34 amino acids rather than the 20 naturally occurring amino acids; custom-engineer two types of building blocks (tRNAs and ribosomes) necessary to make those proteins; and insert the building blocks into a standard lab concoction that contains cell components but no actual cells. There, the components churn out the new proteins without interfering with natural protein-making machinery. "AGENTEX enables researchers to generate entirely new genetic codes on demand in test tubes and use them at scale to build proteins far beyond what nature has evolved," said first author Felix Radford, HMS research fellow in genetics in the Church Lab.
"This is more rapid and safe than existing methods, as it does not rely on handling living cells or altering their genomes." Along the way, the team discovered something unexpected about one of the most fundamental processes of life on Earth: how DNA gets translated into proteins. "It's been really amazing to be working in this environment because not only are we developing new, innovative technologies but we're also discovering new science at the same time," Radford said. All natural life is made of proteins, and proteins are built from combinations of just 20 amino acids.
Each amino acid is encoded by a triplet of DNA or RNA bases called a codon. But there are about three times as many codons as amino acids. For instance, UCU, UCC, UCA and UCG all code for serine.
This redundancy suggests that many codons could be reprogrammed to make something else. After nine years of effort, the Church Lab demonstrated in 2013 that this could be done, freeing up one codon in E. coli bacteria so the microbes could make whatever new amino acid scientists wanted. It took the lab another 10 years to free up a second codon for E. coli to make other new amino acids.
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