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Date
2020-07-24Type
- Journal Article
Citations
Cited 60 times in
Web of Science
Cited 66 times in
Scopus
ETH Bibliography
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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. © 2020 American Association for the Advancement of Science. Show more
Publication status
publishedExternal links
Journal / series
ScienceVolume
Pages / Article No.
Publisher
American Association for the Advancement of ScienceOrganisational unit
03492 - Hilvert, Donald (emeritus) / Hilvert, Donald (emeritus)
08816 - Kast, Peter (Tit.-Prof.)
Funding
182648 - Exploring structure, function, and mechanism of atypical bacterial chorismate mutases (SNF)
176405 - Directed evolution of enzyme structure and function (SNF)
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Show all metadata
Citations
Cited 60 times in
Web of Science
Cited 66 times in
Scopus
ETH Bibliography
yes
Altmetrics