Evolution-based design of chorismate mutase enzymes

Russ, W. P.; Figliuzzi, M.; Stocker, C.; Barrat-Charlaix, P.; Socolich, M.; Kast, P.; Hilvert, D.; Monasson, R.; Cocco, S.; Weigt, M.; Ranganathan, R.

doi:10.1101/2020.04.01.020487

bioRxiv · 10.1101/2020.04.01.020487

Evolution-based design of chorismate mutase enzymes

Russ, W. P.·Figliuzzi, M.·Stocker, C.·Barrat-Charlaix, P.·Socolich, M.·Kast, P.·Hilvert, D.·Monasson, R.·Cocco, S.·Weigt, M.·Ranganathan, R.

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Abstract

The rational design of enzymes is an important goal for both fundamental and practical reasons. Here, we describe a design process in which we learn the constraints for specifying proteins purely from evolutionary sequence data, build libraries of synthetic genes, and test them for activity in vivo using a quantitative complementation assay. For chorismate mutase, a key enzyme in the biosynthesis of aromatic amino acids, we demonstrate the design of natural-like catalytic function with substantial sequence diversity. Further optimization focuses the generative model towards function in a specific genomic context. The data show that sequence-based statistical models suffice to specify proteins and provide access to an enormous space of synthetic functional sequences. This result provides a foundation for a general process for evolution-based design of artificial proteins. One-sentence summaryAn evolution-based, data-driven engineering process can build synthetic functional enzymes.

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Russ, W. P., Figliuzzi, M., Stocker, C., Barrat-Charlaix, P., Socolich, M., Kast, P., Hilvert, D., Monasson, R., Cocco, S., Weigt, M., Ranganathan, R.. 2020-04-02. Evolution-based design of chorismate mutase enzymes. https://doi.org/10.1101/2020.04.01.020487

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