Reprogrammed Ancient Enzyme Could Promote "Greener" Chemistry

A research group at Uppsala University has recreated several billion-year-old enzymes and reprogrammed them to speed up completely different chemical reactions than their modern variants can handle. The method can be used to develop sustainable solutions in biotechnology, for example bioreactors or chemical degradation of environmental toxins. The study has been published in the journal Chemical Science.

We use software to simulate billions of years of evolution and we actually managed to produce an efficient enzyme that can catalyze a whole new reaction. It's incredibly exciting, says Lynn Kamerlin, who leads the research group at Uppsala University.

Enzymes have the ability to catalyze, that is, fast, advanced chemical reactions from millions of years to a fraction of a second without being consumed. They are also biodegradable and have a minimal carbon footprint. Most enzymes are catalysts for a specific chemical reaction and therefore play an important role in biological processes, for example in our bodies.

Quick on unusual reactions

Biotechnology is working intensively to develop new enzymes that can speed up unusual reactions to green chemistry, sustainable production and chemical degradation of environmentally hazardous substances.

The research group at Uppsala University, together with colleagues at the Universidad de Granada in Spain, has reconstructed enzymes that mimic their billions of years old. It was found that the primitive enzymes have many properties desirable in biotechnology; they withstand extreme temperatures and are structurally flexible, making them easier to modify than their modern counterparts.

The researchers succeeded in reprogramming an ancient enzyme to accelerate a completely new reaction, but despite the fact that the new enzyme accelerated the reaction considerably, it was significantly slower than most naturally occurring enzymes.

Used powerful computers

To improve the activity, the researchers used powerful computers to calculate which changes in the structure would produce a faster response. They used a new method called FuncLib, which relies on information on how different enzymes have been developed and how stable they are, to predict more efficient variants.

A total of 3,000 new enzyme structures were developed and the 20 most promising were tested in the lab. Of these, four were significantly faster than the original enzyme. The best was as effective as modern naturally occurring enzymes.

- Our study shows that it is possible to design new, efficient enzymes for a more sustainable society, says Lynn Kamerlin.

Reference
Enhancing a de novo enzyme activity by computationally-focused ultra-low-throughput screening. Valeria A. Risso,  Adrian Romero-Rivera,  Luis I. Gutierrez-Rus,  Mariano Ortega-Muñoz,  Francisco Santoyo-Gonzalez,  Jose A. Gavira,  Jose M. Sanchez-Ruiz and  Shina C. L. Kamerlin. Chem. Sci., 2020, https://doi.org/10.1039/D0SC01935F.

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