An X-ray of the crystal structure of a chain incorporating a beta-linked monomer building block
A molecular chain made by cells with a rewritten genetic code © MRC Laboratory of Molecular Biology

Scientists have broken an “evolutionary deadlock” by genetically engineering microbes with the potential to develop a vast range of new products from drugs to detergents and household plastics.

The researchers at the Medical Research Council Laboratory of Molecular Biology in Cambridge used chemical building blocks that do not occur in the genetic code of living organisms to reprogramme bacterial cells into miniature factories with the ability to synthesise novel substances.

The work is the latest advance in the field of synthetic biology, in which technologies from artificial intelligence to gene editing are being used to explore the development of new materials.

“No one’s ever been able to make these kinds of molecules and alter their sequence in the way we’re able to,” said Jason Chin, the project leader, who expects the largest commercial application to be in pharmaceuticals in the near future. “There will now be a discovery phase that builds on having this technology — and seeing what it can achieve.”

The idea of so-called molecular factories harnesses the basic machinery of sustaining life, in which cells constantly turn out biochemical products. The research repurposes redundant parts of genetic code to instruct the cell to synthesise new materials, while still allowing it to make all the proteins it needs to live.

E. coli under a microscope
Microbes engineered with a new genetic code © MRC Laboratory of Molecular Biology

The latest research, published in Nature on Wednesday, builds on earlier work by Chin’s group to break what the paper dubs an “evolutionary deadlock”.

Previously, the functionality of the engineered microbes was limited because their DNA could only be reprogrammed to produce a small number of amino acids — the building blocks of proteins.

All natural proteins are built from units called alpha-L-amino acids. The team’s breakthrough was to engineer the common E.coli gut microbe so that its genes make other “non-canonical” building blocks such as beta-amino acids and beta-hydroxy acids, which could spur development of a wide range of new polymers.

Polymers, which are composed of chains of similar chemical building blocks, include widely used materials such as polyvinyl chloride, Teflon and Kevlar, as well as biological molecules and enzymes.

The technology also has considerable long-term potential to make novel substances at scale for drugs such as antibiotics, scientists said.

The Cambridge group’s work has started to “open up a door into almost unlimited reprogramming in biology”, said Ben Davis, a professor of chemical biology at Oxford university.

“My strong sense is that this is just the tip of the iceberg of what they will discover,” added Davis, who was not involved in the research.

The Medical Research Council has filed a patent application based on the latest work. The licensee is likely to be Constructive Bio, an LMB spinout founded in 2022 with $15mn seed funding to commercialise the research by Chin’s team.

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