Cambridge scientists create synthetic cells unlike anything in nature – 04/06/2021

Cambridge researchers re-engineered the genetic code of microbes to create a synthetic cell with capabilities unparalleled in nature, opening up the possibility of new materials, from plastics to antibiotics.

The technique of manipulating and editing DNA at the heart of all genetic processes is well established, but until now it has not been possible to modify the 3 billion year old code that DNA uses to instruct cells to make the amino acid chains that make them functional Molecules of life.

“This may be a revolution in biology,” said Jason Chin, project leader at MRC Molecular Biology Laboratory.

“These bacteria can be turned into renewable, programmable factories that produce a wide range of new molecules with new properties that could benefit biotechnology and medicine, including making new drugs such as antibiotics.”

The remarkable research, published in Science magazine, builds on the team’s groundbreaking work in 2019 that created a version of the common microbe in E. coli’s gut, with all of its DNA – known as a genome – completely out Laboratory chemicals.

Scientists have now rewritten the genetic code of the new bacterium Syn61, which not only changes DNA, but also the associated cell machinery that converts genes into biochemicals.

This created a new organism that grows like E. coli, but with additional properties. Groups of three biochemical “letters” – A, T, C, and G – within DNA are key to the process. Each of these “codons” instructs the cell to add a certain amino acid to the growing protein chain. Since the beginning of life on earth, all living things have stored genetic information in this way.

Since there are 64 possible codons and only 20 naturally occurring amino acids, the genetic code has a lot of redundancy. Cambridge scientists took advantage of this by rerouting some codons to produce various building blocks that do not exist in nature, while allowing the cell to produce all of the proteins necessary for life.

An analogy would be to think of nature’s genetic code as an English computer keyboard on which certain letters appear more than once. The Cambridge team actually converted a double A to a Greek alpha letter, an excess B to a beta letter, and so on, making it possible to type in both Greek and English.

Experiments show that modified bacterial cells can bind exotic monomers – molecular building blocks – to form new proteins and other large molecules called polymers.

“We want to use these bacteria to long discover and build synthetic polymers that can fold into structures and form new types of materials,” suggested Chin, adding that another application would be new polymers, such as biodegradable ones Plastics.

Delilah Jewel and Abhishek Chatterjee of Boston College, two leading scientists not involved in Cambridge research, said the technology that uses “unnatural building blocks” would open up numerous new applications, such as “the development of new types of biotherapies and biomaterials with properties of innovative products “. .

One aspect of this technology is that synthetic bacteria are immune to infection by viruses, which require natural genetic processes to reproduce in host cells.

“If a virus gets into the bacterial containers that make certain drugs, it can destroy the entire batch,” Chin said. “Our modified bacterial cells could solve this problem because they are completely resistant to viruses.”

Chin highlighted “great commercial potential” in the microbial engineering process, adding that negotiations to protect intellectual property have already started.

Translated by Luiz Roberto M. Gonçalves

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