ArticleNature communications2021
Metabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 33 citations in OpenAlex.
- Translation accuracy in E. coli.Nucleic acids research · 2026Article
- Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides.Nature communications · 2025Article
- Insights into the regulatory mechanisms and application prospects of the transcription factor Cra.Applied and environmental microbiology · 2024Review
- Synthetic redesign of Escherichia coli W for faster metabolism of sugarcane molasses.Microbial cell factories · 2024Article
- Complex pectin metabolism byFundamental research · 2024Article
- A parallel glycolysis provides a selective advantage through rapid growth acceleration.Nature chemical biology · 2024Article
- A conserved transcription factor controls gluconeogenesis via distinct targets in hypersaline-adapted archaea with diverse metabolic capabilities.PLoS genetics · 2024Article
- The Vibrio cholerae CBASS phage defence system modulates resistance and killing by antifolate antibiotics.Nature microbiology · 2024Article
- UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment.Frontiers in molecular biosciences · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic metabolic pathways are a burden for engineered bacteria, but the underlying mechanisms often remain elusive. Here we show that the misregulated activity of the transcription factor Cra is responsible for the growth burden of glycerol overproducing E. coli. Glycerol production decreases the concentration of fructose-1,6-bisphoshate (FBP), which then activates Cra resulting in the downregulation of glycolytic enzymes and upregulation of gluconeogenesis enzymes. Because cells grow on glucose, the improper activation of gluconeogenesis and the concomitant inhibition of glycolysis likely impairs growth at higher induction of the glycerol pathway. We solve this misregulation by engineering a Cra-binding site in the promoter controlling the expression of the rate limiting enzyme of the glycerol pathway to maintain FBP levels sufficiently high. We show the broad applicability of this approach by engineering Cra-dependent regulation into a set of constitutive and inducible promoters, and use one of them to overproduce carotenoids in E. coli.
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