yETFL Metabolic Model Quiz

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Questions and Answers

What is the name of the model developed for Saccharomyces cerevisiae to integrate expression constraints and reaction thermodynamics?

yETFL

What does yETFL integrate with traditional genome-scale metabolic models?

RNA and protein synthesis

What is the main advantage of yETFL in predicting maximum growth rate and essential genes?

Considerations for biomass composition

What is the primary focus of the model yETFL?

Cell analysis and engineering Signup and view all the answers

What is one limitation of the ETFL model mentioned in the text?

Only applicable for E. coli Signup and view all the answers

What is the potential impact of the presented formulation of yETFL?

Benefit of academic and industrial research Signup and view all the answers

How many unique metabolites are contained in the Yeast822 genome-scale model?

1326 Signup and view all the answers

How many reactions are associated with genes in Yeast822?

2614 Signup and view all the answers

What is the number of enzymes coupled to reactions in the yETFL model?

1059 Signup and view all the answers

How many transporters are associated with transport reactions in the yETFL model?

77 Signup and view all the answers

Does yETFL account for operon structures?

No, but it can include these details in the formulation Signup and view all the answers

How many types of models were developed to study the inclusion/exclusion of thermodynamic constraints and the type of resource allocation?

Four Signup and view all the answers

What type of framework does yETFL use to model metabolism?

Constraint-based optimization framework Signup and view all the answers

What does yETFL predict in terms of biomass composition and transcription/translation machinery content?

Growth-condition-dependent biomass composition and machinery content Signup and view all the answers

How does yETFL differ from WM_S288C in expression modeling?

yETFL uses constraint-based optimization framework, while WM_S288C uses ordinary differential equations Signup and view all the answers

What does yETFL predict about the shift in growth conditions?

A shift from glucose-limited growth to proteome-limited growth Signup and view all the answers

What is the predicted maximum growth rate for E(T)FL.cb according to yETFL?

0.44 h extsuperscript{-1} Signup and view all the answers

What caused small discrepancies between experimental data and yETFL results?

Glucose uptake rates Signup and view all the answers

What is the main challenge in engineering eukaryotic organisms for industrial biotechnology?

Compartmentalized cell structure Signup and view all the answers

Which method is introduced to overcome some of the issues with Flux Balance Analysis (FBA)?

Thermodynamic-based flux balance analysis (TFA) Signup and view all the answers

What is the new approach called that includes the cellular expression system in addition to metabolic and catalytic constraints?

Expression and Thermodynamics-enabled Flux (ETFL) Signup and view all the answers

What is the yETFL model specifically developed for?

S. cerevisiae, accounting for the additional ribosomes and RNA polymerases within the eukaryotic mitochondrial expression system Signup and view all the answers

What do the methodological advancements in ETFL provide avenues for?

Development of similar models for the study of other eukaryotes Signup and view all the answers

What is the implication of the advancement in modeling eukaryotic organisms for industrial biotechnology?

Production of fuels, chemicals, and therapeutic proteins Signup and view all the answers

What does yETFL use for feasible solution space and growth-dependent parameters?

Highest reported ribosomal elongation rate Signup and view all the answers

Which model successfully predicts shifts in metabolic fluxes at high growth rates, capturing the Crabtree effect?

yETFL Signup and view all the answers

What does yETFL predict more genes corresponding to compared to the FBA model?

RNA polymerases and ribosomes Signup and view all the answers

What does the integration of thermodynamic constraints into FBA or EFL.cb models not change?

Essentiality results Signup and view all the answers

Which models present earlier onset of Crabtree effect relative to E[T]FL.cb models?

E[T]FL.vb models Signup and view all the answers

What is affected by models with higher protein ratios?

Maximum growth rate and onset of Crabtree effect Signup and view all the answers

Study Notes

Yeast Metabolic Model yETFL Predicts Gene Essentiality and Crabtree Effect

yETFL uses highest reported ribosomal elongation rate for feasible solution space and growth-dependent parameters
Regulatory system in S. cerevisiae drives metabolism towards optimality
Gene essentiality analysis shows identical results for yETFL, EFL.cb, and FBA models for metabolic genes
yETFL predicts more genes corresponding to RNA polymerases and ribosomes compared to FBA model
Integration of thermodynamic constraints into FBA or EFL.cb does not change essentiality results
Crabtree effect, or overflow metabolism, observed in S. cerevisiae at high growth rates
yETFL successfully predicts shifts in metabolic fluxes at high growth rates, capturing the Crabtree effect
yETFL considers limitations in catalytic capacity of enzymes and protein expression machinery
Model shows good qualitative agreement with experimental data from aerobic, glucose-limited chemostat cultures
E[T]FL.vb models present earlier onset of Crabtree effect relative to E[T]FL.cb models
Models with higher protein ratios are less tightly constrained, affecting maximum growth rate and onset of Crabtree effect
Slight deviation between model predictions and experimental observations in transition region for growth rates between 0.3 and 0.36 h−1

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