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Journal Articles Science Year : 2020

An evolution-based model for designing chorismate mutase enzymes

William Russ
Matteo Figliuzzi
Christian Stocker
Pierre Barrat-Charlaix
  • Function : Author
Michael Socolich
  • Function : Author
Peter Kast
Donald Hilvert
Remi Monasson
Simona Cocco
Rama Ranganathan

Abstract

The rational design of enzymes is an important goal for both fundamental and practical reasons. Here, we describe a process to learn the constraints for specifying proteins purely from evolutionary sequence data, design and 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 toward 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 functional sequences. This result provides a foundation for a general process for evolution-based design of artificial proteins.
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hal-04028834 , version 1 (14-03-2023)

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William Russ, Matteo Figliuzzi, Christian Stocker, Pierre Barrat-Charlaix, Michael Socolich, et al.. An evolution-based model for designing chorismate mutase enzymes. Science, 2020, 369 (6502), pp.440-445. ⟨10.1126/science.aba3304⟩. ⟨hal-04028834⟩
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