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An evolution-based model for designing chorismate mutase enzymes.
Journal article

An evolution-based model for designing chorismate mutase enzymes.

  • Russ WP University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Figliuzzi M Sorbonne Université, CNRS, Institut de Biologie Paris Seine, Laboratoire de Biologie Computationnelle and Quantitative, Paris, France.
  • Stocker C Laboratory of Organic Chemistry, ETH Zurich, Switzerland.
  • Barrat-Charlaix P Sorbonne Université, CNRS, Institut de Biologie Paris Seine, Laboratoire de Biologie Computationnelle and Quantitative, Paris, France.
  • Socolich M Center for Physics of Evolving Systems, Biochemistry and Molecular Biology and the Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Kast P Laboratory of Organic Chemistry, ETH Zurich, Switzerland.
  • Hilvert D Laboratory of Organic Chemistry, ETH Zurich, Switzerland.
  • Monasson R Laboratoire de Physique de l'Ecole Normale Supérieure, PSL and CNRS, Paris, France.
  • Cocco S Laboratoire de Physique de l'Ecole Normale Supérieure, PSL and CNRS, Paris, France.
  • Weigt M Sorbonne Université, CNRS, Institut de Biologie Paris Seine, Laboratoire de Biologie Computationnelle and Quantitative, Paris, France. ranganathanr@uchicago.edu martin.weigt@upmc.fr.
  • Ranganathan R Center for Physics of Evolving Systems, Biochemistry and Molecular Biology and the Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA. ranganathanr@uchicago.edu martin.weigt@upmc.fr.
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  • 2020-07-25
Published in:
  • Science (New York, N.Y.). - 2020
Amino Acid Sequence
Chorismate Mutase
Escherichia coli Proteins
Evolution, Molecular
Models, Genetic
Models, Statistical
English 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.
Language
  • English
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Persistent URL
https://sonar.ch/global/documents/200068
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