Fungal aerobic reductive dechlorination of ethyl 2-chloroacetoacetate by Saccharomyces cerevisiae: mechanism of a novel type of microbial dehalogenation.
Saccharomyces cerevisiae reduces the beta-keto ester ethyl 2-chloroacetoacetate to the respective chiral cis- and trans-beta-hydroxy esters. In the course of chiral reduction, competing dehalogenation of the xenobiotic substrate to ethyl acetoacetate occurs, in a reaction mediated by cytosolic glutathione (GSH). Mechanistically, the dechlorination is a novel type of glutathione-dependent dehalogenation catalysed by an as yet unidentified glutathione-dependent dehalogenase. The first step consists of a nucleophilic replacement of the chloride substituent by glutathione. In the subsequent enzyme-catalysed step, a second glutathione molecule liberates the dehalogenation product by thiolytic attack at the thioether bridge, resulting in a net transfer of two electrons to the substrate and in the formation of glutathione disulfide (GSSG). Being effective under aerobic conditions and catalysed by a fungus, this reductive dechlorination of an aliphatic substrate is an outstanding example of a novel, glutathione-mediated microbial dehalogenation.
Jörg
Gerhard
G
Technische Universität Dresden, Institut für Biochemie, 01062 Dresden, Germany.
Bertau
Martin
M
D000090:Acetoacetates / Q000378:metabolism*; D000332:Aerobiosis; D000818:Animals; D001711:Biotransformation; D002712:Chlorides / Q000378:metabolism*; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006736:Horses; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D000090:Acetoacetates; D002712:Chlorides; D004791:Enzyme Inhibitors; C111982:ethyl 4-chloro-3-oxobutanoate; D005982:Glutathione Transferase; D005978:Glutathione