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[GT] Designing an irreversible metabolic switch for scalable induction of microbial chemical production

Mankind uses chemicals for almost everything, from food preservatives to pharmaceuticals to cosmetics to biofuels. It essential to seek alternative ways to manufacture chemicals, on an industrial-scale, sustainably and cheaply - paving the way to a greener cleaner future.

As we¡¯ve reported in previous issues, high-value chemicals used in biofuels and pharmaceuticals can be made from bacteria by switching their chemistry to produce novel products. Now, researchers from the University of Warwick have found a way to drastically cut the cost of turning on these switches.

Bacteria can be seen as nature¡¯s micro-chemical factories, and many researchers are trying to understand how their complex network of chemical reactions can be re-wired to convert cheap feedstock like glucose into high-value chemical products for our use. Using genetic switches to redirect the bacteria¡¯s chemistry is an exciting development in the field of Synthetic Biology.

Typically, genetic switches are turned on by adding a chemical called an inducer. However, inducers are expensive, and often need to be constantly added to prevent switching back off, analogous to a ¡°light switch with a spring in it¡± that turns back off when you let go. This makes this switching approach expensive and so scaling up to industrial production is economically infeasible.

Using mathematical models and the engineering principles of feedback control loops, commonly used in flight control systems, the researchers discovered how to design a genetic switch in bacteria that removes the reverting ¡°spring,¡± so that adding only a pulse of a cheap natural nutrient can switch the cell to chemical production mode permanently - drastically cutting costs.

The ability to switch bacteria into chemical production mode permanently is a massive step forward to realizing the economically viable scale up of chemical production from microbes.

This switch should be widely applicable to many industrially relevant microbes for the synthesis of almost any chemical. The next steps of our research would be to uncover the principles to understand where in the chemical roadmap to apply this ¡°traffic light¡± and perhaps look to collaborating with industry where it could be readily incorporated into existing fermentation processes.

Using cutting-edge synthetic biology techniques this work has laid out the framework for constructing the proposed irreversible switch in the lab. Not only could this work change the way chemical industries make high-value chemicals, it also contributes to the larger vision for how humans can move away from reliance on non-renewable resources, to enabling sustainable synthesis of biochemicals, for a greener and cleaner future.

NATURE COMMUNICATIONS, June 8, 2021, ¡°Designing an irreversible metabolic switch for scalable induction of microbial chemical production,¡± by Ahmad A. Mannan, Declan G. Bates. © 2021 Springer Nature Limited. All rights reserved.

To view or purchase this article, please visit: 
https://www.nature.com/articles/s41467021-23606-x





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- NATURE COMMUNICATIONS, June 8, 2021, ¡°Designing an irreversible metabolic switch for scalable induction of microbial chemical production,¡± by Ahmad A. Mannan, Declan G. Bates. © 2021 Springer Nature Limited. All rights reserved.

To view or purchase this article, please visit: 
https://www.nature.com/articles/s41467021-23606-x