ArticlePLoS computational biology2014
Optimizing metabolite production using periodic oscillations.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 23 citations in OpenAlex.
- Exploring the Potential of Cell-Free Protein Synthesis for Extending the Abilities of Biological Systems.Frontiers in bioengineering and biotechnology · 2019Review
- Dynamic metabolic engineering: New strategies for developing responsive cell factories.Biotechnology journal · 2015Review
- A Chemical Engineer's Perspective on Health and Disease.Computers & chemical engineering · 2014Article
- Recent advances and opportunities in synthetic logic gates engineering in living cells.Systems and synthetic biology · 2014Review
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Authors and funding
3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Methods for improving microbial strains for metabolite production remain the subject of constant research. Traditionally, metabolic tuning has been mostly limited to knockouts or overexpression of pathway genes and regulators. In this paper, we establish a new method to control metabolism by inducing optimally tuned time-oscillations in the levels of selected clusters of enzymes, as an alternative strategy to increase the production of a desired metabolite. Using an established kinetic model of the central carbon metabolism of Escherichia coli, we formulate this concept as a dynamic optimization problem over an extended, but finite time horizon. Total production of a metabolite of interest (in this case, phosphoenolpyruvate, PEP) is established as the objective function and time-varying concentrations of the cellular enzymes are used as decision variables. We observe that by varying, in an optimal fashion, levels of key enzymes in time, PEP production increases significantly compared to the unoptimized system. We demonstrate that oscillations can improve metabolic output in experimentally feasible synthetic circuits.
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