Metabolic enzyme cost explains variable trade-offs between microbial growth rate and yield

Area of Science:

• Microbial metabolism
• Systems biology
• Biochemical engineering

Background:

• Microbes balance growth rate versus biomass yield, often exhibiting a trade-off between speed and efficiency.
• Fast growth typically correlates with less efficient, higher-cost metabolism.
• A thermodynamic trade-off between growth rate and biomass yield is a proposed explanation.

Purpose of the Study:

• To investigate the relationship between microbial growth rate and biomass yield.
• To explore the universality of the growth rate/yield trade-off.
• To utilize a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM), for metabolic analysis.

Main Methods:

• Developed and applied the Enzyme-Flux Cost Minimization (EFCM) modeling framework.
• Constructed a comprehensive mathematical model of core metabolism in Escherichia coli.
• Screened all elementary flux modes for cell synthesis to characterize growth rates and yields.
• Analyzed the Pareto front of rate/yield trade-offs under varying conditions.

Main Results:

• The growth rate/yield trade-off is not universal and depends on metabolic kinetics and environmental factors.
• Under oxygen-limited conditions, yield-inefficient pathways yield 2-3 times higher growth rates than yield-efficient pathways.
• The study characterized the Pareto front of achievable growth rates and yields.

Conclusions:

• EFCM provides a powerful tool for predicting optimal metabolic states and growth rates.
• The framework is applicable to diverse scenarios, including varying nutrient levels and genetic perturbations.
• Metabolic efficiency and growth rate optimization are context-dependent, particularly under specific environmental stresses like oxygen limitation.