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 threat-ens most organisms (in humans MG causes diabetes). MG is predominantly detoxified by the glyoxalase pathway. This process begins with the conjugation of MG with gluta-thione (GSH), yielding a hemithioacetal product that is subsequently transformed by the glyoxalase enzymes intoD-lactate and GSH. MG has been overlooked in photosynthetic organisms, although they inevitably produce it not only by the catabolism of sugars, lip-ids, and amino acids, as do heterotrophic organisms, but also by their active photoau-totrophic metabolism. This is especially true for cyanobacteria that are regarded as hav-ing developed photosynthesis and GSH-dependent enzymes to detoxify the reactive oxygen species produced by their photosynthesis (CO2 assimilation) and respiration (glu-cose 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 en-zymes. 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 reac-tion, always regarded as nonenzymatic, could exist in plants and/or human and thus have an impact on agriculture and/or human health.