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Cambridge researchers have rethought the genetic code of microbes to create a synthetic cell with capabilities different from anything in nature, opening up the possibility of new materials for everything from plastics to antibiotics.
The knowledge of how to manipulate and edit DNA is at the heart of all genetic processes is established, but so far it has not been possible to modify the 3 billion year code through which DNA instructs cells. cells to form the amino acid chains that make up the working molecules of life.
“This is potentially a revolution in biology,” said Jason Chin, project leader of the MRC Molecular Biology Laboratory.
“These bacteria can become renewable and programmable factories that produce a wide range of new molecules with new properties, which could have benefits for biotechnology and medicine, including the manufacture of new drugs such as antibiotics.”
The emblematic research, published in the journal Science, is based on the team’s 2019 advance who created a version of the common E. coli intestinal microbe with all its DNA, known as the genome, built entirely from laboratory chemicals.
Scientists have rewritten the genetic code of the new Syn61 bacterium that altered not only DNA, but also the associated cellular machinery that converts genes into biochemicals. This created a new organism that grows like E. coli but with additional properties.
The key to the process is the groups of three biochemical “letters” (A, T, C, and G) within DNA. Each of these “codons” tells the cell to add a specific amino acid to the growing protein chain. Since the dawn of life on Earth, all creatures have stored genetic information in this way.
Jason Chin has proposed a range of applications for the technology, including new drugs and biodegradable plastics © MRC-LMB
Because there are 64 possible codons and only 20 natural amino acids, the genetic code has a lot of redundancy. Cambridge scientists have taken advantage of this by reusing some codons to produce different building blocks that do not exist in nature, although they allow the cell to make all the proteins necessary for life.
An analogy would be to see the genetic code of nature as a computer keyboard in English in which certain letters appear more than once. In fact, the Cambridge team has converted a duplicate A into the Greek letter alpha, a surplus B into beta, etc., allowing it to be written in both Greek and English.
Experiments show that designed bacterial cells can chain exotic monomers (molecular blocks) into new proteins and other large molecules known as polymers.
“We would like to use these bacteria to discover and build long synthetic polymers that fold into structures and can form new kinds of materials,” Chin proposed, adding that another application would be new polymers such as biodegradable plastics.
Delilah Jewel and Abhishek Chatterjee of Boston College, two leading scientists not involved in the Cambridge research, said the technology using “unnatural building blocks” would unlock countless new applications, “since the development of new biotherapy classes even biomaterials with innovative properties. ”
One aspect of the technology is that synthetic bacteria are impervious to virus infection, which require natural genetic processes to replicate in host cells.
“If a virus enters the tubs of bacteria that are used to make certain drugs, then it can destroy the entire batch,” Chin explained. “Our modified bacterial cells could overcome this problem by being completely resistant to viruses.”
Chin highlighted “great commercial potential” in the microbial engineering process, adding that talks had been held to protect intellectual property.
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