Metabolic Flux Analysis (MFA)
MFA studies are carried out by feeding cells a non-radioactive isotopically labeled substrate (e.g., C-labeled glucose) and subsequently measuring the patterns of stable isotope incorporation that emerge in downstream metabolites using LC-MS, GC-MS, and NMR.
A computational model of the intracellular metabolic network is used to determine pathway fluxes by integrating these isotope labeling data with additional measurements of extracellular nutrient uptake and product excretion rates.
By systematically accounting for all extracellular carbon inputs and outputs and all major intracellular pathways, MFA can be used to reconstruct comprehensive flux maps depicting cell metabolism.
Comparison of flux maps obtained under varying experimental conditions or in the presence of targeted genetic manipulations provides a functional readout on the global impact these perturbations have on cell metabolism.
CoreMFA technology and software are customized to each customer’s application, facilitating the visualization and interpretation of actionable results.
Enables identification and elimination of bottlenecks, metabolic inefficiencies and wasteful byproduct pathways in industrial host organisms, markedly enhancing cell factory production rates and yields.
Allows users to optimize cell line and culture media development and enables selection of clones and/or conditions for high titer recombinant protein production.
Metabolic flux map of lactate-consuming phase. The magnitude of each net carbon flux corresponds with the color and width of each reaction arrow. [N. Templeton, A. Lewis, H. Dorai, E.A. Qian, M.P. Campbell, K.D. Smith, S.E. Lang, M.J. Betenbaugh, J.D. Young. The impact of anti-apoptotic gene Bcl-2 Δ expression on CHO central metabolism. Metabolic Engineering 25:92-102, 2014.]
Saves time and money: reduces time to achieving maximal efficiency and productivity, increases revenues and profitability.
1) Develop metabolic network model
2) Optimize tracers and measurements
3) Perform isotope labeling experiment
4) Measure extracellular exchange rates and
C isotopomer abunances
5) Apply C MFA to estimate fluxes
Each CoreMFA model is customized to each customer’s application and facilitates the visualization and interpretation of results. CoreMFA identifies bottlenecks and other metabolic inefficiencies and provides actionable results to the customer.
Atomic-level Metabolite Measurement
The platform uses a non-radioactive, stable isotope to provide atomic-level details that are easier to interpret.
Small Sample Sizes
The process requires only a small number of samples, which reduces the cost of producing samples and data analysis.
Dynamic View of Metabolism
CoreMFA can visualize the rate at which metabolism is proceeding in measured pathways; thus, investigators can control these rates with processes, nutrients and/or genetic engineering to improve quality and quantity of output.
Compare Process Variables
Metabolic maps with an overlay of flux rates allow investigators to easily compare multiple process variables to improve output.
CoreMFA can evaluate alternative process conditions after the baseline model has been validated, which reduces the time and cost to optimize process conditions for different cell lines and/or products.