Metabolite secretion in microorganisms: the theory of metabolic overflow put to the test

Abstract

Introduction Microbial cells secrete many metabolites during growth, including important intermediates of the central carbon metabolism. This has not been taken into account by researchers when modeling microbial metabolism for metabolic engineering and systems biology studies. Materials and MethodsThe uptake of metabolites by microorganisms is well studied, but our knowledge of how and why they secrete different intracellular compounds is poor. The secretion of metabolites by microbial cells has traditionally been regarded as a consequence of intracellular metabolic overflow. Conclusions Here, we provide evidence based on time-series metabolomics data that microbial cells eliminate some metabolites in response to environmental cues, independent of metabolic overflow. Moreover, we review the different mechanisms of metabolite secretion and explore how this knowledge can benefit metabolic modeling and engineering.

Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models

“…GEMs do not explicitly consider regulation, whose effects are better reflected in the global transcriptome and the metabolome. [10][11][12][13][14] FBA approaches have been extended with RNAseq and metabolomics data to capture cell regulation and more accurately describe cellular metabolic behavior. 15 For example, transcriptional regulation of gene expression has been linked to GEMs, either by taking into account the absolute expression values, scoring genes and subsequently reaction fluxes as active or non-active based on their expression, [16][17][18] or by incorporating relative gene-expression.…”

“…15 For example, transcriptional regulation of gene expression has been linked to GEMs, either by taking into account the absolute expression values, scoring genes and subsequently reaction fluxes as active or non-active based on their expression, [16][17][18] or by incorporating relative gene-expression. 14,18 Use of relative gene expression is assuming that the relative changes between two conditions correlate with the resulting differential flux profiles. Both approaches can lead to conditionspecific GEMs that are more effective for inferring the actual biochemical activity and the observed physiology of the microorganism.…”

The Role of Purified α-amylase from Soil Bacteria Versus Crude Cell Supernatant from Medium against Clinical Biofilm-forming Bacteria

“…The results showed greatest inhibition obtained by B. circulans against K. pneumoniae biofilm with percentage of 93.6% and the lowest inhibition recorded by B. cereus against P. aeruginosa biofilm with percentage of 21.7%. This may be due to presence of some extracellular and intracellular metabolites in the medium where intracellular can release into extracellular medium when accumulated in the cell and this has been explained by the metabolic overflow theory [47][48][49].…”

Microbial metabolomics: essential definitions and the importance of cultivation conditions for utilizing Bacillus species as bionematicides

“…) due to imbalanced intracellular metabolic pathways (Pinu et al . ). In response to environmental conditions, metabolite secretion can be seen as a fundamental biochemical function which reflects the internal metabolic state of microbial cells.…”

“…Yet, it has been observed that metabolites which do not accumulate within the cell are directly excreted into the extracellular medium in response to environmental signals (Pinu et al . ).…”