Validated In Silico Population Model of Escherichia coli

Flux balance analysis (FBA) and ordinary differential equation models have been instrumental in depicting the metabolic functioning of a cell. Nevertheless, they demonstrate a population’s average behavior (summation of individuals), thereby portraying homogeneity. However, living organisms such as Escherichia coli contain more biochemical reactions than engaging metabolites, making them an underdetermined and degenerate system. This results in a heterogeneous population with varying metabolic patterns. We have formulated a population systems biology model that predicts this degeneracy by emulating a diverse metabolic makeup with unique biochemical signatures. The model mimics the universally accepted experimental view that a subpopulation of bacteria, even under normal growth conditions, renders a unique biochemical state, leading to the synthesis of metabolites and persister progenitors of antibiotic resistance and biofilms. We validate the platform’s predictions by producing commercially important heterologous (isobutanol) and homologous (shikimate) metabolites. The predicted fluxes are tested in vitro resulting in 32- and 42-fold increased product of isobutanol and shikimate, respectively. Moreover, we authenticate the platform by mimicking a bacterial population in the presence of glyphosate, a metabolic pathway inhibitor. Here, we observe a fraction of subsisting persisters despite inhibition, thus affirming the signature of a heterogeneous populace. The platform has multiple uses based on the disposition of the user.

• Publication year

  2022

• Venue

  ACS Synthetic Biology

• Publication date

  2022-07-08

• Fields of study

  Biology, Medicine, Computer Science, Engineering

• Identifiers
  DOI 10.1021/acssynbio.2c00097PMID 35801944PMCID 9397402
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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