Hacking the genetic code opens the door to advanced materials

Researchers at Cambridge have re-engineered the genetic code of microbes to create an artificial cell with capabilities unlike anything in nature, opening up the possibility of new materials for everything from plastics to antibiotics.

Knowledge of how DNA is manipulated and edited has been established at the heart of all genetic processes, but until now it has not been possible to alter the 3-billion-year-old code by which DNA directs cells to form the chains of amino acids that make up the working molecules of life.

“This is potentially a revolution in biology,” said Jason Chen, project leader at the MRC Laboratory of Molecular Biology.

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

Historical research published in the journal Science, builds on the team for 2019 breakthrough that created a copy of the common coli bacteria The gut bacteria with its entire DNA — known as its genome — is built entirely from chemicals in the lab.

Scientists have now rewrote the genetic code of a new Syn61 bacterium that has changed not only the DNA but also the associated cellular machinery that turns genes into biochemical products. This created a new organism that grows like coli bacteria But with additional properties.

The key to the process is the combinations of three biochemical “letters” – A, T, C and G – within the 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 suggested a range of applications for this technology including new medicines and biodegradable plastics © MRC-LMB

With 64 potential codons and only 20 naturally occurring amino acids, the genetic code has a lot of redundancy. Cambridge scientists took advantage of this by reusing some of the codons to produce different building blocks not found in nature while allowing the cell to make all the proteins needed for life.

An analogy would be seeing the genetic code of nature as a computer keyboard in English on which certain letters appear more than once. The Cambridge team, in fact, converted a duplicate of A to the Greek letter alpha, overflow B to beta and so on, making it possible to write both in Greek and in English.

Experiments show that engineered bacterial cells can bind foreign monomers – the molecular building 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 can fold into structures and may form new classes of materials,” Chen suggested, adding that another application would be new polymers such as biodegradable plastics.

Technology that uses “unnatural building blocks” will open up countless new applications, “from developing new classes of biotherapies to biomaterials with innovative properties,” said Delilah Jewel and Abhishek Chatterjee of Boston College, two prominent scientists who were not involved in the Cambridge research. .”

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

“If a virus gets into the pools of bacteria used to make some drugs, it can destroy the entire population,” Chen explained. “Our modified bacterial cells can overcome this problem by being completely resistant to viruses.”

Chen highlighted “a lot of commercial potential” for the microbial engineering process, adding that talks had taken place to protect intellectual property.

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