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Chemoselective Henry Condensations Catalyzed by Artificial Carboligases
Author(s) -
Garrabou Xavier,
Macdonald Duncan Stuart,
Hilvert Donald
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201605757
Subject(s) - chemoselectivity , nitromethane , directed evolution , catalysis , chemistry , atp synthase , active site , enzyme , combinatorial chemistry , biochemistry , computational biology , stereochemistry , biology , organic chemistry , gene , mutant
The promiscuity of de novo designed enzymes provides a privileged platform for diverse abiological reactions. In this work, we report the first example of a nitroolefin synthase that catalyzes the Henry condensation between aromatic aldehydes and nitromethane. Significant catalytic activity was discovered in the computationally designed and evolved carboligase RA95.5‐8, and mutations around the active site were shown to improve the reaction rate, demonstrating the potential to optimize the enzyme by directed evolution. This novel nitroolefin synthase could participate in complex biological cascades, whereby the highly tunable chemoselectivity could afford useful synthetic building blocks.