World’s first artificial enzymes created using synthetic biology

UK-based scientists have created the world’s first enzymes made from artificial genetic material.

The breakthrough work conducted by the Medical Research Council confirms its place as one of the leading developers of synthetic biology, one of the most exciting and cutting edge areas of biotechnology today.

Synthetic biology is still in its infancy, but has huge potential across a wide range of applications, from creating new foods or biofuels, as well as novel highly-targeted medicines.

The synthetic enzymes have been made from molecules that do not occur anywhere in nature, and could be the foundation for an entirely new generation of drugs and diagnostics.

The research, published today in Nature, gives new insights into the origins of life. The work suggest that genetic information can be stored in molecules other than DNA and RNA, as previously assumed.

The findings build on previous work by the team at the MRC Laboratory of Molecular Biology, which saw them create synthetic molecules called ‘XNAs’ that can store and pass on genetic information, in a similar way to DNA.

Using their lab-made XNAs as building blocks, the team has now created ‘XNAzymes’, which power simple reactions, such as cutting up or stitching together small chunks of RNA, just like naturally occurring enzymes.

In 2012, a group led by Dr Philipp Holliger, head of the MRC’s Laboratory of Molecular Biology, showed that six alternative XNAs could also store genetic information and evolve through natural selection. They have now expanded on this principle to discover, for the first time, four different types of synthetic catalyst formed from these entirely unnatural building blocks.

The XNAzymes are capable of catalysing simple reactions like cutting and joining RNA strands in a test tube. One of the XNAzymes can even join XNA strands together, which represents one of the first steps to creating a living system.

Dr Holliger commented: “Our XNAs are chemically extremely robust and, because they do not occur in nature, they are not recognised by the body’s natural degrading enzymes. This might make them an attractive candidate for long-lasting treatments that can disrupt disease-related RNAs.”

Professor Patrick Maxwell, Chair of the MRC’s Molecular and Cellular Medicine Board, said:

“Synthetic biology is delivering some truly amazing advances that promise to change the way we understand and treat disease. The UK excels in this field, and this latest advance offers the tantalising prospect of using designer biological parts as a starting point for an entirely new class of therapies and diagnostic tools that are more effective and have a longer shelf-life.”

Funders of this work included the MRC, European Science Foundation and the Biotechnology and Biological Sciences Research Council.

The MRC’s tax-funded work has frequently formed the basis of work for the discovery and development of new drugs, including AbbVie’s Humira, currently the biggest selling drug in the world.

Researchers around world are looking at practical applications for synthetic biology, with a number of for-profit firms working towards commercialising the technology. One such firm is US-based Synlogic a biotech company focused on the development of therapeutic microbes.

The UK government wants to help foster new synthetic biology companies, and has set up a $75 million Industrial Biotechnology Catalyst which has been established by the Biotechnology and Biological Sciences Research Council (BBSRC), the Technology Strategy Board (now renamed Innovate UK) and the Engineering and Physical Sciences Research Council (EPSRC). The Catalyst fund will address the major technical challenges biological processes, or processes in which biological and chemical approaches are used in combination.

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