An ATP and oxalate generating variant tricarboxylic acid cycle counters aluminum toxicity in Pseudomonas fluorescens.
Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al). The increased activity of succinyl-CoA synthetase (SCS) and oxalate CoA-transferase (OCT) in the Al-stressed cells afforded an effective route to ATP synthesis from oxalyl-CoA via substrate level phosphorylation. This modified TCA cycle with diminished efficacy in NADH production and decreased CO(2)-evolving capacity, orchestrates the synthesis of oxalate, NADPH, and ATP, ingredients pivotal to the survival of P. fluorescens in an Al environment. The channeling of succinyl-CoA towards ATP formation may be an important function of the TCA cycle during anaerobiosis, Fe starvation and O(2)-limited conditions.
Singh
Ranji
R
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada.
Lemire
Joseph
J
Mailloux
Ryan J
RJ
Chénier
Daniel
D
Hamel
Robert
R
Appanna
Vasu D
VD
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D002952:Citric Acid Cycle; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic; D006418:Heme / Q000737:chemistry; D007522:Isocitrate Lyase / Q000378:metabolism; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D010070:Oxalates / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011551:Pseudomonas fluorescens / Q000187:drug effects*
D010070:Oxalates; D006418:Heme; D009249:NADP; D000255:Adenosine Triphosphate; D000535:Aluminum; D000445:Aldehyde Oxidoreductases; C040590:glyoxylate dehydrogenase (acylating); D007522:Isocitrate Lyase; D010100:Oxygen