Methylglyoxal Detoxification Revisited: Role of Glutathione Transferase in Model Cyanobacterium Synechocystis sp. Strain PCC 6803

Abstract

Methylglyoxal (MG) is a detrimental metabolic by-product that threatens most organisms (in humans MG causes diabetes). MG is predominantly detoxified by the glyoxalase pathway. This process begins with the conjugation of MG with glutathione (GSH), yielding a hemithioacetal product that is subsequently transformed by the glyoxalase enzymes into d-lactate and GSH. MG has been overlooked in photosynthetic organisms, although they inevitably produce it not only by the catabolism of sugars, lipids, and amino acids, as do heterotrophic organisms, but also by their active photoautotrophic metabolism. This is especially true for cyanobacteria that are regarded as having developed photosynthesis and GSH-dependent enzymes to detoxify the reactive oxygen species produced by their photosynthesis (CO2 assimilation) and respiration (glucose catabolism), which they perform in the same cell compartment. In this study, we used a combination of in vivo and in vitro approaches to characterize a logical, but as yet never described, link between MG detoxification and a (prokaryotic) representative of the evolutionarily conserved glutathione transferase (GST) detoxification enzymes. We show that the Sll0067 GST of the model cyanobacterium Synechocystis sp. strain PCC 6803 plays a prominent role in MG tolerance and detoxification, unlike the other five GSTs of this organism. Sll0067 catalyzes the conjugation of MG with GSH to initiate its elimination driven by glyoxalases. These results are novel because the conjugation of MG with GSH is always described as nonenzymatic. They will certainly stimulate the analysis of Sll0067 orthologs from other organisms with possible impacts on human health (development of biomarkers or drugs) and/or agriculture. IMPORTANCE In most organisms, methylglyoxal (MG), a toxic metabolite by-product that causes diabetes in humans, is predominantly detoxified by the glyoxalase enzymes. This process begins with the so-called “spontaneous” conjugation of MG with the cytoprotectant metabolite glutathione (GSH). In this study, we unravel a logical, but as yet unsuspected, link between MG detoxification and a (prokaryotic) representative of the ubiquitous glutathione transferase (GST) enzymes. We show that a GST of a model cyanobacterium plays a prominent role in the detoxification of MG in catalyzing its conjugation with GSH. This finding is important because this reaction, always regarded as nonenzymatic, could exist in plants and/or human and thus have an impact on agriculture and/or human health.

Glutathione Metabolism in Plants under Stress: Beyond Reactive Oxygen Species Detoxification

“…In the photosynthetic prokaryote Synechocystis sp. strain PCC6803, one of the six glutathione-S transferases (GST Sll0067; EC 2.5.1.1.8), catalyses the conjugation of GSH with MG to form HTA, the starting point in MG detoxification by the GLX pathway [ 170 ]. This is interesting since HTA is always reported as being formed non-enzymatically from the spontaneous nucleophilic reaction between GSH and MG in both prokaryotes [ 171 ] and eukaryotes [ 172 , 173 ].…”

Color recycling: metabolization of apocarotenoid degradation products suggests carbon regeneration via primary metabolic pathways

“…Both RCS have also been identified as in vitro degradation products of β-carotene under exposure to oxygen or ozone (Benevides et al 2011;Mogg and Burton 2020). The main sources of methylglyoxal and glyoxal in planta have so far been considered sugar autoxidation, lipid peroxidation and, for the former of the two, especially glycolysis (Schümperli et al 2007;Paudel et al 2016;Kammerscheit et al 2020). However, biochemical and transcriptional evidence excluded lipid peroxidation, a known major source of methylglyoxal and glyoxal, as the cause for the observed accumulation of both RCS in apocarotenoid-accumulating Arabidopsis roots (Yanishlieva et al 1998;Koschmieder et al 2020).…”

Genetic, Genomics, and Responses to Stresses in Cyanobacteria: Biotechnological Implications

“…Sll0067 operates in the protection against methylglyoxal (MG), a toxic metabolite by-product of the catabolism of sugars, lipids, and amino-acids, which causes diabetes in human. Sll0067 catalyzes the conjugation of GSH with MG, the first step in MG detoxification catalyzed by the glyoxalase enzymes [ 145 ].…”