Laboratory evolution reveals a two-dimensional rate-yield tradeoff in microbial metabolism

Area of Science:

• Microbial Physiology
• Systems Biology
• Computational Biology

Background:

• Growth rate and yield are key microbial characteristics, but their mechanistic relationship is poorly understood.
• Existing models often simplify rate-yield tradeoffs, failing to explain observed phenotypic diversity in adapted microbes like Escherichia coli.
• Maintenance energy and proteome allocation are known factors influencing these tradeoffs.

Purpose of the Study:

• To identify and mechanistically explain a more complex, two-dimensional rate-yield tradeoff in adapted Escherichia coli strains.
• To develop a quantitative, multi-scale model for describing the full rate-yield relationship.
• To uncover specific metabolic mechanisms underlying these tradeoffs.

Main Methods:

• Utilized a multi-scale modeling approach combining a coarse-grained proteome allocation model with a fine-grained genome-scale metabolic and gene expression (ME) model.
• Applied the model to Escherichia coli K-12 MG1655.
• Analyzed the interplay between growth rate, yield, substrate uptake rate, and metabolic flux allocation.

Main Results:

• Identified a two-dimensional rate-yield tradeoff: (A) growth rate vs. yield, and (B) glucose uptake rate vs. growth yield.
• Developed a quantitative model that resolves the complexity of ME-models for proteome analysis.
• Proposed modifications to the P/O ratio and altered flux distribution in glycolysis and the pentose phosphate pathway (PPP) as mechanisms enabling the glucose uptake rate-growth yield tradeoff.

Conclusions:

• Microbial rate-yield tradeoffs are more complex than previously understood, involving multiple dimensions.
• A multi-scale modeling approach provides mechanistic insights into these complex relationships.
• Metabolic regulation, including P/O ratio and flux allocation, plays a crucial role in microbial adaptation and resource utilization.