TY  - JOUR
AU  - Borah Slater, Khushboo
AU  - Beyß, Martin
AU  - Xu, Ye
AU  - Barber, Jim
AU  - Costa, Catia
AU  - Newcombe, Jane
AU  - Theorell, Axel
AU  - Bailey, Melanie J
AU  - Beste, Dany J V
AU  - McFadden, Johnjoe
AU  - Nöh, Katharina
TI  - One-shot 13 C15 N-metabolic flux analysis for simultaneous quantification of carbon and nitrogen flux.
JO  - Molecular systems biology
VL  - 19
IS  - 3
SN  - 1744-4292
CY  - Heidelberg
PB  - EMBO Press
M1  - FZJ-2023-01361
SP  - e11099
PY  - 2023
AB  - 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.
KW  - Bayesian metabolic flux analysis (Other)
KW  - Mycobacterium tuberculosis (Other)
KW  - carbon metabolism (Other)
KW  - isotope labeling (Other)
KW  - nitrogen metabolism (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36705093
UR  - <Go to ISI:>//WOS:000945787300001
DO  - DOI:10.15252/msb.202211099
UR  - https://juser.fz-juelich.de/record/1005173
ER  -