We use protein engineering and directed evolution to adapt natural enzymes for new applications.

The challenge

Unusual microbes: lots of potential, but difficult to work with

Many enzymes need cofactors to work. These are small molecules that are needed for enzyme’s to perform chemical reactions – in fact, many of the vitamins that we need in our diets are cofactors. Some cofactors are found in every living thing (e.g. adenosine triphosphate, ATP), but some cofactors are only found in a few difficult to grow microbes, such as the obscure cofactor F420.

Cofactor F420 is found in only a few types of microbes and is used in a number of interesting biological processes: turning carbon dioxide into methane; making antibiotics and even allowing bacteria to ‘eat’ the explosive TNT. There are lots of applications for microbes and enzymes that use cofactor F420, but as the microbes that make cofactor F420 are challenging and slow to grow, it’s difficult and uneconomic to use them in these applications.

Cofactor F420, a small molecule that enables some microbes to do unusual and useful chemistry.

Our response

Teaching a laboratory bacterium a new biochemical trick

In a collaboration with Prof. Colin Jackson’s group at the Australian National University, we have trained the fast growing laboratory bacterium Escherichia coli to be able to make cofactor F420. We have done this by taking the enzymes that make this unusual cofactor from a number of different microbes and transplanting them into Escherichia coli.

The results

Accessing novel biochemistry

The new Escherichia coli strain can make cofactor F420 and we have been able to further modify the strain so that it can use the cofactor to perform chemical reactions that depend upon this cofactor. We hope that this new strain will be used as a tool for chemical synthesis, in remediation of contaminants such as TNT and in the laboratory to understand processes such as methane production.

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