Burden-aware feedback control of microbial consortia
File(s)
Published version
Author(s)
Boo, Alice
Mehta, Harman
Ledesma-Amaro, Rodrigo
Stan, Guy
Type
Journal Article
Abstract
Engineered microbial consortia are emerging as programmable systems capable of sensing and responding to their environment. However, maintaining defined community composition over time remains challenging, particularly in bioprocesses where growth conditions and metabolic burdens continuously shift. Here, we develop a burden-aware multicellular RNA-based feedback control system that stabilises coculture composition by coupling gene expression burden to growth regulation. The system integrates three modules: quorum sensing-based communication, an RNA-based comparator computing deviations from a target ratio, and tuneable growth regulation via heterologous expression burden or CRISPRi-mediated knockdowns. In a two-strain E. coli coculture, this architecture maintains stable coculture ratios over 24-hour batch cultures, recovers growth rates by up to 90% following burden-induced growth reduction, and increases protein production yields by up to 81% in the slower-growing strain. We achieve tuneability by adjusting RNA binding strength and quorum-sensing signal production. This work demonstrates that burden-driven growth control can be used to stabilise and tune synthetic microbial consortia.
Date Issued
2026-05-06
Date Acceptance
2026-04-15
Citation
Nature Communications, 2026, 17
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
17
Copyright Statement
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41467-026-72389-6
Publication Status
Published
Article Number
6100
Date Publish Online
2026-05-06