Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold
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Date
2021-03Type
- Journal Article
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Cited 24 times in
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Cited 26 times in
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Abstract
New enzyme catalysts are usually engineered by repurposing the active sites of natural proteins. Here we show that design and directed evolution can be used to transform a non-natural, functionally naive zinc-binding protein into a highly active catalyst for an abiological hetero-Diels–Alder reaction. The artificial metalloenzyme achieves >104 turnovers per active site, exerts absolute control over reaction pathway and product stereochemistry, and displays a catalytic proficiency (1/KTS = 2.9 × 1010 M−1) that exceeds all previously characterized Diels–Alderases. These properties capitalize on effective Lewis acid catalysis, a chemical strategy for accelerating Diels–Alder reactions common in the laboratory but so far unknown in nature. Extension of this approach to other metal ions and other de novo scaffolds may propel the design field in exciting new directions. Show more
Publication status
publishedExternal links
Journal / series
Nature ChemistryVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03492 - Hilvert, Donald (emeritus) / Hilvert, Donald (emeritus)
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Show all metadata
Citations
Cited 24 times in
Web of Science
Cited 26 times in
Scopus
ETH Bibliography
yes
Altmetrics