ArticleNature communications2016
A dynamic pathway analysis approach reveals a limiting futile cycle in N-acetylglucosamine overproducing Bacillus subtilis.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 58 citations in OpenAlex.
- Facilitating stable gene integration expression and copy number amplification inSynthetic and systems biotechnology · 2024Article
- Reprogramming Metabolic Flux in Escherichia Coli to Enhance Chondroitin Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Design of a sorbitol-activated nitrogen metabolism-dependent regulatory system for redirection of carbon metabolism flow in Bacillus licheniformis.Nucleic acids research · 2023Article
- A Programmable CRISPR/Cas9 Toolkit Improves Lycopene Production in Bacillus subtilis.Applied and environmental microbiology · 2023Article
- CRISPR-dCas12a-mediated genetic circuit cascades for multiplexed pathway optimization.Nature chemical biology · 2023Article
- Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.Cell reports · 2021Article
- Titrating bacterial growth and chemical biosynthesis for efficient N-acetylglucosamine and N-acetylneuraminic acid bioproduction.Nature communications · 2020Article
- Tracing metabolic flux through time and space with isotope labeling experiments.Current opinion in biotechnology · 2020Review
- Selective and Accurate Quantification ofAnalytical chemistry · 2020Article
- Design of a programmable biosensor-CRISPRi genetic circuits for dynamic and autonomous dual-control of metabolic flux in Bacillus subtilis.Nucleic acids research · 2020Article
- Engineering the transmission efficiency of the noncyclic glyoxylate pathway for fumarate production inBiotechnology for biofuels · 2020Article
- Genome-driven cell engineering review:Essays in biochemistry · 2019Review
- Modular pathway engineering of key precursor supply pathways for lacto-Biotechnology for biofuels · 2019Article
- Synthetic biology strategies for improving microbial synthesis of "green" biopolymers.The Journal of biological chemistry · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advances in genome engineering have further widened the gap between our ability to implement essentially any genetic change and understanding the impact of these changes on cellular function. We lack efficient methods to diagnose limiting steps in engineered pathways. Here, we develop a generally applicable approach to reveal limiting steps within a synthetic pathway. It is based on monitoring metabolite dynamics and simplified kinetic modelling to differentiate between putative causes of limiting product synthesis during the start-up phase of the pathway with near-maximal rates. We examine the synthetic N-acetylglucosamine (GlcNAc) pathway in Bacillus subtilis and find none of the acetyl-, amine- or glucose-moiety precursors to limit synthesis. Our dynamic metabolomics approach predicts an energy-dissipating futile cycle between GlcNAc6P and GlcNAc as the primary problem in the pathway. Deletion of the responsible glucokinase more than doubles GlcNAc productivity by restoring healthy growth of the overproducing strain.
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