title: Chemoselective Henry Condensations Catalyzed by Artificial Carboligases.
abstract: 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.
authors.affiliation: Laboratory of Organic Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
authors.forename: Xavier
authors.identifier: http://orcid.org/0000-0003-3663-8420
authors.initials: X
authors.lastname: Garrabou
authors.affiliation: Laboratory of Organic Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
authors.forename: Duncan Stuart
authors.initials: DS
authors.lastname: Macdonald
authors.affiliation: Laboratory of Organic Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009595:Nitroparaffins / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D009595:Nitroparaffins; D005634:Fructose-Bisphosphate Aldolase; D008697:Methane; C008640:nitromethane
keywords: Henry reaction; artificial enzymes; directed evolution; enzyme catalysis; nitrostyrene