The role of glyoxalase I in the detoxification of methylglyoxal and in the activation of the KefB K⁺ efflux system in Escherichia coli

Abstract

SummaryThe glyoxalase I gene (gloA) of Escherichia coli has been cloned and used to create a null mutant. Cells overexpressing glyoxalase I exhibit enhanced tolerance of methylglyoxal (MG) and exhibit elevated rates of detoxification, although the increase is not stoichiometric with the change in enzyme activity. Potassium efflux via KefB is also enhanced in the overexpressing strain. Analysis of the physiology of the mutant has revealed that growth and viability are quite normal, unless the cell is challenged with MG either added exogenously or synthesized by the cells. The mutant strain has a low rate of detoxification of MG, and cells rapidly lose viability when exposed to this electrophile. Activation of KefB and KefC is diminished in the absence of functional glyoxalase I. These data suggest that the glutathione-dependent glyoxalase I is the dominant detoxification pathway for MG in E. coli and that the product of glyoxalase I activity, S-lactoylglutathione, is the activator of KefB and KefC.

Complex Transcriptional Control Links NikABCDE-Dependent Nickel Transport with Hydrogenase Expression in Escherichia coli

“…Glyoxalase I (GlxI), has maximal activity in vitro in the presence of nickel ions (11,13,15,35). This enzyme, which detoxifies methylglyoxal produced from dihydroxyacetone phosphate, is expressed under aerobic growth conditions (20) and thus requires an independent source of nickel for its activity. This source of nickel may also be important for NikR function.…”

GlpD and PlsB Participate in Persister Cell Formation in Escherichia coli

“…MG synthesis is a glycolytic bypass that leads to pyruvate via DHAP and MG (Fig. 4) (1,11,22,36). DHAP is the product of GlpD-catalyzed dehydrogenation of G3P, and one would expect that an increase in DHAP would lead to an increase in MG, which could in turn produce dormancy.…”

Transcriptional Activation of the Aldehyde Reductase YqhD by YqhC and Its Implication in Glyoxal Metabolism of Escherichia coli K-12

“…Unlike GO, detoxification of MG is quite well characterized and is known to involve the glyoxalase system and AKRs (11,13,32,34,35). The glyoxalase system consists of glyoxalases I and II (gloA and gloB, respectively), which require GSH as a cofactor (16,36), and which produce lactate from MG. The AKRs, including YafB, YqhE, and YghZ, are also reported to detoxify MG by generating hydroxyacetone using NADPH (13).…”