title: Evaluation of the Substrate Scope of Benzoic Acid (De)carboxylases According to Chemical and Biochemical Parameters.
abstract: The enzymatic carboxylation of phenolic compounds has been attracting increasing interest in recent years, owing to its regioselectivity and technical potential as a biocatalytic equivalent for the Kolbe-Schmitt reaction. Mechanistically the reaction was demonstrated to occur through electrophilic aromatic substitution/water elimination with bicarbonate as a cosubstrate. The effects of the substituents on the phenolic ring have not yet been elucidated in detail, but this would give detailed insight into the substrate-activity relationship and would provide predictability for the acceptance of future substrates. In this report we show how the kinetic and (apparent) thermodynamic behavior can be explained through the evaluation of linear free energy relationships based on electronic, steric, and geometric parameters and through the consideration of enzyme-ligand interactions. Moreover, the similarity between the benzoic acid decarboxylases and the amidohydrolases superfamily is investigated, and promiscuous hydrolytic activity of the decarboxylase in the context of the hydrolysis of an activated ester bond has been established.
authors: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestrasse 15, 21073, Hamburg, Germany.
authors: Lorenzo
authors: L
authors: Pesci
authors: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestrasse 15, 21073, Hamburg, Germany.
authors: Selin
authors: S
authors: Kara
authors: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestrasse 15, 21073, Hamburg, Germany. liese@tuhh.de.
authors: Andreas
authors: A
authors: Liese
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000737:chemistry / Q000378:metabolism*; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D004952:Esters; D010636:Phenols; D019817:Benzoic Acid; D002262:Carboxy-Lyases
keywords: QSAR; carboxylation; enzymatic Kolbe-Schmitt reaction; enzyme catalysis; phenolic acids; zinc-dependent enzymes