Achieving metabolic flux analysis for S. cerevisiae at a genome-scale: Challenges, requirements, and considerations

Saratram Gopalakrishnan, Costas D. Maranas

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


Recent advances in 13C-Metabolic flux analysis (13C-MFA) have increased its capability to accurately resolve fluxes using a genome-scale model with narrow confidence intervals without pre-judging the activity or inactivity of alternate metabolic pathways. However, the necessary precautions, computational challenges, and minimum data requirements for successful analysis remain poorly established. This review aims to establish the necessary guidelines for performing 13C-MFA at the genome-scale for a compartmentalized eukaryotic system such as yeast in terms of model and data requirements, while addressing key issues such as statistical analysis and network complexity. We describe the various approaches used to simplify the genome-scale model in the absence of sufficient experimental flux measurements, the availability and generation of reaction atom mapping information, and the experimental flux and metabolite labeling distribution measurements to ensure statistical validity of the obtained flux distribution. Organism-specific challenges such as the impact of compartmentalization of metabolism, variability of biomass composition, and the cell-cycle dependence of metabolism are discussed. Identification of errors arising from incorrect gene annotation and suggested alternate routes using MFA are also highlighted.

Original languageEnglish (US)
Pages (from-to)521-535
Number of pages15
Issue number3
StatePublished - Sep 18 2015

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology


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