ArticlePLoS computational biology2018
Metabolic enzyme cost explains variable trade-offs between microbial growth rate and yield.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed.
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- Biocalorimetry for the biotechnological use of natural and synthetic macromolecules.Applied microbiology and biotechnology · 2026Review
- Enzyme Catalytic Parameters and Evolution Across the Dissipation Plane.International journal of molecular sciences · 2026Review
- COBRA-k: A powerful framework bridging constraint-based and kinetic metabolic modeling.Science advances · 2026Article
- Microbial carbon fixation pathways shifts during artificialFrontiers in microbiology · 2026Article
- D- and L-lactate consumers are taxonomically, biochemically, and energetically different.ISME communications · 2026Article
- A compact model of Escherichia coli core and biosynthetic metabolism.PLoS computational biology · 2025Article
- Balancing Cell Growth and Product Synthesis for Efficient Microbial Cell Factories.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Construction and Characterization of MoClo-Compatible Vectors for Modular Protein Expression inACS synthetic biology · 2025Article
- Metabolic Objectives and Trade-Offs: Inference and Applications.Metabolites · 2025Review
- Inferring metabolic objectives and trade-offs in single cells during embryogenesis.Cell systems · 2025Article
- Life history strategies complement niche partitioning to support the coexistence of closely related Gilliamella species in the bee gut.The ISME journal · 2025Article
- Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy.Heliyon · 2024Article
- Assembly of functional microbial ecosystems: from molecular circuits to communities.FEMS microbiology reviews · 2024Review
- Free-energy transduction mechanisms shape the flux space of metabolic networks.Biophysical journal · 2024Article
- Mitochondrial ATP generation is more proteome efficient than glycolysis.Nature chemical biology · 2024Article
- Non-thermodynamic factors affect competition between thermophilic chemolithoautotrophs from deep-sea hydrothermal vents.Applied and environmental microbiology · 2024Article
- Including glutamine in a resource allocation model of energy metabolism in cancer and yeast cells.NPJ systems biology and applications · 2024Article
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Authors and funding
5 authors.
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Abstract
Microbes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production. In a comprehensive mathematical model of core metabolism in E. coli, we screened all elementary flux modes leading to cell synthesis, characterized them by the growth rates and yields they provide, and studied the shape of the resulting rate/yield Pareto front. By varying the model parameters, we found that the rate/yield trade-off is not universal, but depends on metabolic kinetics and environmental conditions. A prominent trade-off emerges under oxygen-limited growth, where yield-inefficient pathways support a 2-to-3 times higher growth rate than yield-efficient pathways. EFCM can be widely used to predict optimal metabolic states and growth rates under varying nutrient levels, perturbations of enzyme parameters, and single or multiple gene knockouts.
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