Deciphering and harnessing promoter-driven feedback controllers to mitigate metabolic burden in Corynebacterium glutamicum
Journal article, 2026
Metabolic burden arises from the reallocation of cellular resources, often resulting in stress-associated phenotypes and compromised cellular performance. However, the molecular mechanisms by which industrial microorganisms perceive and alleviate such burdens remain largely unexplored. Here, we present an online monitor to quantify metabolic burden imposed by genetic and environmental perturbations in the workhorse Corynebacterium glutamicum. RNA-seq analysis revealed a shared host response and enabled the identification of several early-responsive promoters through in vivo burden assays. Leveraging these elements, particularly the cg1940 promoter, we successfully engineered dynamic feedback systems to alleviate metabolic burden associated with suboptimal expression. Notably, the identified promoter retained burden responsiveness in Escherichia coli, suggesting potential cross-species applicability. As a proof of concept, this feedback controller was applied to improve cell growth, protein synthesis, and chemical bioproduction. This technology offers a strategy for bolstering the robustness of C. glutamicum and potentially other microorganisms.
feedback regulation
metabolic burden
burden-responsive promoters
C. glutamicum
Author
Hongyu Zhang
Tianjin Institute of Industrial Biotechnology
Chinese Academy of Sciences
Zhongxin Zhang
College of Biological and Agricultural Engineering
Yanan Chen
Tianjin Institute of Industrial Biotechnology
Chinese Academy of Sciences
Lingcong Li
Chinese Academy of Sciences
Tianjin Institute of Industrial Biotechnology
Jiwei Mao
Chalmers, Life Sciences, Systems and Synthetic Biology
Liang Wei
National Technology Innovation Center of Synthetic Biology
Tianjin Institute of Industrial Biotechnology
Jian Wang
College of Biological and Agricultural Engineering
Yan Zhu
Tianjin Institute of Industrial Biotechnology
National Technology Innovation Center of Synthetic Biology
Yun Chen
Chalmers, Life Sciences, Systems and Synthetic Biology
Jens B Nielsen
Chalmers, Life Sciences, Systems and Synthetic Biology
BioInnovation Institute
Ning Xu
Chinese Academy of Sciences
Tianjin Institute of Industrial Biotechnology
National Technology Innovation Center of Synthetic Biology
Jun Liu
Chinese Academy of Sciences
National Technology Innovation Center of Synthetic Biology
Tianjin Institute of Industrial Biotechnology
Trends in Biotechnology
0167-7799 (ISSN) 18793096 (eISSN)
Vol. In PressSubject Categories (SSIF 2025)
Microbiology
DOI
10.1016/j.tibtech.2026.02.020
PubMed
41945032