D-2-Hydroxyglutarate dehydrogenase plays a dual role in L-serine biosynthesis and D-malate utilization in the bacterium Pseudomonas stutzeri

Pseudomonas is a very large bacterial genus in which several species can use D-malate for growth. However, the enzymes that can metabolize D-malate, such as D-malate dehydrogenase, appear to be absent in most Pseudomonas species. D-3-Phosphoglycerate dehydrogenase (SerA) can catalyze the production of D-2-hydroxyglutarate (D-2-HG) from 2-ketoglutarate to support D-3-phosphoglycerate dehydrogenation, which is the initial reaction in bacterial L-serine biosynthesis. In this study, we show that SerA of the Pseudomonas stutzeri strain A1501 reduces oxaloacetate to D-malate and that D-2-HG dehydrogenase (D2HGDH) from P. stutzeri displays D-malate-oxidizing activity. Of note,D2HGDHparticipates in converting a trace amount of D-malate to oxaloacetate during bacterial L-serine biosynthesis. Moreover,D2HGDHis crucial for the utilization of D-malate as the sole carbon source for growth of P. stutzeri A1501. We also found that theD2HGDHexpression is induced by the exogenously added D-2-HG or D-malate and that a flavoprotein functions as a soluble electron carrier between D2HGDH and electron transport chains to support D-malate utilization by P. stutzeri. These results support the idea thatD2HGDHevolves as an enzyme for both D-malate and D-2-HG dehydrogenation in P. stutzeri. In summary, D2HGDH from P. stutzeri A1501 participates in both a core metabolic pathway for L-serine biosynthesis and utilization of extracellular D-malate.