Structural highlights
Publication Abstract from PubMed
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 >10(4) turnovers per active site, exerts absolute control over reaction pathway and product stereochemistry, and displays a catalytic proficiency (1/KTS = 2.9 x 10(10) 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.
Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold.,Basler S, Studer S, Zou Y, Mori T, Ota Y, Camus A, Bunzel HA, Helgeson RC, Houk KN, Jimenez-Oses G, Hilvert D Nat Chem. 2021 Mar;13(3):231-235. doi: 10.1038/s41557-020-00628-4. Epub 2021 Feb , 1. PMID:33526894[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Basler S, Studer S, Zou Y, Mori T, Ota Y, Camus A, Bunzel HA, Helgeson RC, Houk KN, Jimenez-Oses G, Hilvert D. Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold. Nat Chem. 2021 Mar;13(3):231-235. doi: 10.1038/s41557-020-00628-4. Epub 2021 Feb , 1. PMID:33526894 doi:http://dx.doi.org/10.1038/s41557-020-00628-4
