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@ARTICLE{BorahSlater:1005173,
      author       = {Borah Slater, Khushboo and Beyß, Martin and Xu, Ye and
                      Barber, Jim and Costa, Catia and Newcombe, Jane and
                      Theorell, Axel and Bailey, Melanie J and Beste, Dany J V and
                      McFadden, Johnjoe and Nöh, Katharina},
      title        = {{O}ne-shot 13 {C}15 {N}-metabolic flux analysis for
                      simultaneous quantification of carbon and nitrogen flux.},
      journal      = {Molecular systems biology},
      volume       = {19},
      number       = {3},
      issn         = {1744-4292},
      address      = {Heidelberg},
      publisher    = {EMBO Press},
      reportid     = {FZJ-2023-01361},
      pages        = {e11099},
      year         = {2023},
      abstract     = {Metabolic flux is the final output of cellular regulation
                      and has been extensively studied for carbon but much less is
                      known about nitrogen, which is another important building
                      block for living organisms. For the tuberculosis pathogen,
                      this is particularly important in informing the development
                      of effective drugs targeting the pathogen's metabolism. Here
                      we performed 13 C15 N dual isotopic labeling of
                      Mycobacterium bovis BCG steady state cultures, quantified
                      intracellular carbon and nitrogen fluxes and inferred
                      reaction bidirectionalities. This was achieved by model
                      scope extension and refinement, implemented in a multi-atom
                      transition model, within the statistical framework of
                      Bayesian model averaging (BMA). Using BMA-based 13 C15
                      N-metabolic flux analysis, we jointly resolve carbon and
                      nitrogen fluxes quantitatively. We provide the first
                      nitrogen flux distributions for amino acid and nucleotide
                      biosynthesis in mycobacteria and establish glutamate as the
                      central node for nitrogen metabolism. We improved resolution
                      of the notoriously elusive anaplerotic node in central
                      carbon metabolism and revealed possible operation modes. Our
                      study provides a powerful and statistically rigorous
                      platform to simultaneously infer carbon and nitrogen
                      metabolism in any biological system.},
      keywords     = {Bayesian metabolic flux analysis (Other) / Mycobacterium
                      tuberculosis (Other) / carbon metabolism (Other) / isotope
                      labeling (Other) / nitrogen metabolism (Other)},
      cin          = {IBG-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2171 - Biological and environmental resources for
                      sustainable use (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2171},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36705093},
      UT           = {WOS:000945787300001},
      doi          = {10.15252/msb.202211099},
      url          = {https://juser.fz-juelich.de/record/1005173},
}