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Microbial cooperation involves beneficial interactions in which different species work together for individual or mutual advantage. These interactions can profoundly influence ecological dynamics and evolutionary processes, and they are essential to many pathogenic and symbiotic relationships.Nematode–Bacteria CooperationA striking example is the relationship between the Gram-negative bacterium Xenorhabdus nematophila and the parasitic nematode Steinernema carpocapsae. Juvenile nematodes...
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Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
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Prospecting Microbial Strains for Bioremediation and Probiotics Development for Metaorganism Research and Preservation
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Burden-aware feedback control of microbial consortia.

Alice Boo1,2, Harman Mehta1,2, Rodrigo Ledesma-Amaro3,4,5,6

  • 1Imperial College Centre for Excellence in Synthetic Biology, Imperial College London, London, SW7 2AZ, UK.

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Summary

We developed an RNA-based control system to stabilize engineered microbial consortia. This system couples gene expression burden to growth regulation, maintaining stable ratios and improving protein yields in synthetic biology applications.

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Area of Science:

  • Synthetic Biology
  • Microbial Ecology
  • Genetic Engineering

Background:

  • Engineered microbial consortia offer programmable environmental sensing and response.
  • Maintaining stable community composition in dynamic bioprocesses is a significant challenge due to shifting growth conditions and metabolic burdens.

Purpose of the Study:

  • To develop a multicellular RNA-based feedback control system for stabilizing coculture composition.
  • To investigate the coupling of gene expression burden to growth regulation for maintaining defined microbial ratios.

Main Methods:

  • Implemented a burden-aware multicellular RNA-based feedback control system.
  • Integrated quorum sensing communication, an RNA-based comparator for ratio deviation, and tuneable growth regulation via heterologous expression burden or CRISPRi.
  • Utilized a two-strain *E. coli* coculture model for experimental validation.

Main Results:

  • Achieved stable coculture ratios over 24-hour batch cultures.
  • Demonstrated recovery of growth rates by up to 90% after burden-induced reduction.
  • Increased protein production yields by up to 81% in the slower-growing strain.
  • Showcased tuneability by adjusting RNA binding strength and quorum-sensing signal production.

Conclusions:

  • Burden-driven growth control is an effective strategy for stabilizing synthetic microbial consortia.
  • The developed RNA-based system enables robust control and tuning of microbial community composition.
  • This approach enhances the reliability and productivity of engineered microbial systems.