Researchers in Cambridge have re-engineered the genetic code of microbes to create a synthetic cell with capabilities unlike anything in nature, opening up the possibility of new materials for everything from plastics to antibiotics.
The knowledge of how to manipulate and edit the DNA at the heart of all genetic processes is established, but until now it has not been possible to alter the 3bn-year-old code through which DNA instructs 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 Chin, project leader at the MRC Laboratory of Molecular Biology.
“These bacteria may be turned into renewable and 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.”
The landmark research, published in the journal Science, builds on the team’s 2019 breakthrough that created a version of the common E. coli gut microbe with all its DNA — known as the genome — constructed entirely from lab chemicals.
The scientists have now rewritten the genetic code of the new Syn61 bacterium that altered not only the DNA but also the associated cellular machinery that turns genes into biochemical products. This created a new organism that grows like E. coli but with additional properties.
Key to the process are groups 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 of Earth all creatures have stored genetic information in this way.
Because there are 64 possible codons and only 20 naturally occurring amino acids, the genetic code has a lot of redundancy. The Cambridge scientists have exploited this by repurposing some codons to produce different building blocks that do not exist in nature while still allowing the cell to make all the proteins required for life.
An analogy would be to see nature’s genetic code as an English language computer keyboard on which certain letters appear more than once. The Cambridge team has, in effect, converted a duplicate A into the Greek letter alpha, a surplus B into a beta and so on, making it possible to type in Greek as well as English.
The experiments show that engineered bacterial cells can string together exotic monomers — molecular building blocks — into novel proteins and other large molecules known as polymers.
“We would like to use these bacteria to discover and build long synthetic polymers that fold up into structures and may form new classes of materials,” Chin proposed, adding that another application would be novel polymers such as biodegradable plastics.
Delilah Jewel and Abhishek Chatterjee of Boston College, two leading scientists not involved in the Cambridge research, said technology using “non-natural building blocks” would unlock countless new applications, “from the development of new classes of biotherapeutics to biomaterials with innovative properties.”
One aspect of the technology is that synthetic bacteria are impervious to infection by viruses, which require natural genetic processes to replicate in host cells.
“If a virus gets into the vats of bacteria used to manufacture certain drugs then it can destroy the whole batch,” Chin explained. “Our modified bacterial cells could overcome this problem by being completely resistant to viruses.”
Chin highlighted “a lot of commercial potential” to the microbial engineering process, adding that talks to protect intellectual property had taken place.