ArticleNature communications2018
Diverse genetic error modes constrain large-scale bio-based production.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
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- Simultaneous optimization of lignocellulosic sugar catabolism via systematic laboratory evolution under complex selection pressure.Nature communications · 2026Article
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- Kinetic modeling of terpenoid production in E. coli: insights into subpopulation emergence and process optimization.Microbial cell factories · 2025Article
- Enhanced genetic stability and expression control in growth-decoupled continuous two-stage E. coli fermentations using plasmid-dependent thyA auxotrophic selection.Microbial cell factories · 2025Article
- Exploring single-cell biosynthetic noise and dynamics for enhanced betaxanthin production in Escherichia coli.Nature communications · 2025Article
- Programmable cell differentiation in budding yeast uncouples reproductive and metabolic tasks.bioRxiv : the preprint server for biology · 2025Article
- Biosensor-driven strain engineering reveals key cellular processes for maximizing isoprenol production inScience advances · 2025Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- Review
- Influence of Different Transposon Families on Genomic Stability of Shewanella oneidensis MR1.Microbial biotechnology · 2025Article
- Reduced Genetic Heterogeneity for Stable Bioproduction by Harnessing the Bias and Mechanism of Mutation.Microbial biotechnology · 2025Article
- Codon usage modulates the relationship between the burden and yield of protein overexpression.Journal of biological engineering · 2025Article
- The generation game: Toward the generational genetic stability of continuous culture.iScience · 2025Article
- An automated high-throughput lighting system for screening photosynthetic microorganisms in plate-based formats.Communications biology · 2025Article
- Increased Mevalonate Production Using Engineered Citrate Synthase and Phosphofructokinase Variants of Escherichia coli.Biotechnology and bioengineering · 2025Article
- Microbial Production of High-Performance Fibers from Muscle Protein Titin.Methods in molecular biology (Clifton, N.J.) · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A transition toward sustainable bio-based chemical production is important for green growth. However, productivity and yield frequently decrease as large-scale microbial fermentation progresses, commonly ascribed to phenotypic variation. Yet, given the high metabolic burden and toxicities, evolutionary processes may also constrain bio-based production. We experimentally simulate large-scale fermentation with mevalonic acid-producing Escherichia coli. By tracking growth rate and production, we uncover how populations fully sacrifice production to gain fitness within 70 generations. Using ultra-deep (>1000×) time-lapse sequencing of the pathway populations, we identify multiple recurring intra-pathway genetic error modes. This genetic heterogeneity is only detected using deep-sequencing and new population-level bioinformatics, suggesting that the problem is underestimated. A quantitative model explains the population dynamics based on enrichment of spontaneous mutant cells. We validate our model by tuning production load and escape rate of the production host and apply multiple orthogonal strategies for postponing genetically driven production declines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.