Systems-level metabolic flux profiling elucidates a complete, bifurcated tricarboxylic acid cycle in Clostridium acetobutylicum.

Journal of Bacteriology
Daniel Amador-NoguezJoshua D Rabinowitz

Abstract

Obligatory anaerobic bacteria are major contributors to the overall metabolism of soil and the human gut. The metabolic pathways of these bacteria remain, however, poorly understood. Using isotope tracers, mass spectrometry, and quantitative flux modeling, here we directly map the metabolic pathways of Clostridium acetobutylicum, a soil bacterium whose major fermentation products include the biofuels butanol and hydrogen. While genome annotation suggests the absence of most tricarboxylic acid (TCA) cycle enzymes, our results demonstrate that this bacterium has a complete, albeit bifurcated, TCA cycle; oxaloacetate flows to succinate both through citrate/alpha-ketoglutarate and via malate/fumarate. Our investigations also yielded insights into the pathways utilized for glucose catabolism and amino acid biosynthesis and revealed that the organism's one-carbon metabolism is distinct from that of model microbes, involving reversible pyruvate decarboxylation and the use of pyruvate as the one-carbon donor for biosynthetic reactions. This study represents the first in vivo characterization of the TCA cycle and central metabolism of C. acetobutylicum. Our results establish a role for the full TCA cycle in an obligatory anaerobic organ...Continue Reading

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Citations

Aug 8, 2012·Molecular BioSystems·Jan HuegeBjörn H Junker
Jan 11, 2011·Applied and Environmental Microbiology·Shaohua WangYin Li
Sep 29, 2011·Applied and Environmental Microbiology·Daniel Amador-NoguezJoshua D Rabinowitz
Jan 3, 2012·Applied and Environmental Microbiology·Joungmin LeeSang Yup Lee
Jul 26, 2011·Journal of Bacteriology·Ernest Marco-UrreaLorenz Adrian
Sep 19, 2014·Microbial Cell Factories·Matthew D ServinskyChristian J Sund
Dec 10, 2015·Bioprocess and Biosystems Engineering·Roberto GallardoGermán Aroca
Dec 19, 2012·Metabolic Engineering·Scott B Crown, Maciek R Antoniewicz
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Apr 8, 2011·Bioresource Technology·Mona Abo-HasheshPatrick C Hallenbeck
Mar 8, 2011·Current Opinion in Biotechnology·Tina Lütke-Eversloh, Hubert Bahl
Dec 25, 2015·Biotechnology for Biofuels·Meng-Lei XiaHong-Zhang Chen
Sep 1, 2015·Current Opinion in Biotechnology·Maciek R Antoniewicz
Sep 18, 2015·MicrobiologyOpen·Samantha S SasnowLudmilla Aristilde
Dec 8, 2014·Microbiology·Christian J SundMargaret M Hurley
Jun 17, 2014·Metabolic Engineering·Stéphanie HeuxJean-Charles Portais
Apr 17, 2016·Current Opinion in Biotechnology·Lorenz Adrian, Ernest Marco-Urrea
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Jul 13, 2014·Current Opinion in Microbiology·Bree B Aldridge, Kyu Y Rhee
Jun 12, 2012·Plant Science : an International Journal of Experimental Plant Biology·Eva CollakovaRyan S Senger

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