ArticleApplied and environmental microbiology2015
Polar Fixation of Plasmids during Recombinant Protein Production in Bacillus megaterium Results in Population Heterogeneity.
Article in Applied and environmental microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Toward food-grade production of the Bacteroides helcogenes protein-glutamine glutaminase with an optimized Bacillus subtilis strain.Applied microbiology and biotechnology · 2026Article
- Single cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity.Nature communications · 2025Article
- Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology.Synthetic and systems biotechnology · 2025Review
- Exploring auxotrophy and engineering vitamin BApplied and environmental microbiology · 2024Article
- Protein secretion zones during overexpression of amylase within the Gram-positive cell wall.BMC biology · 2023Article
- Fixation dynamics of beneficial alleles in prokaryotic polyploid chromosomes and plasmids.Genetics · 2022Article
- The effect of droplet size on syntrophic dynamics in droplet-enabled microbial co-cultivation.PloS one · 2022Article
- Segregational Drift Constrains the Evolutionary Rate of Prokaryotic Plasmids.Molecular biology and evolution · 2021Article
- The "beauty in the beast"-the multiple uses of Priestia megaterium in biotechnology.Applied microbiology and biotechnology · 2021Review
- Effect of Photocaged Isopropyl β-d-1-thiogalactopyranoside Solubility on the Light Responsiveness of LacI-controlled Expression Systems in Different Bacteria.Chembiochem : a European journal of chemical biology · 2021Article
- Optimized gene expression from bacterial chromosome by high-throughput integration and screening.Science advances · 2021Article
- Response surface methodology based optimization and scale-up production of amylase from a novel bacterial strain,Biotechnology reports (Amsterdam, Netherlands) · 2020Article
- Bacterial metabolic heterogeneity: origins and applications in engineering and infectious disease.Current opinion in biotechnology · 2020Review
- Emergence of plasmid stability under non-selective conditions maintains antibiotic resistance.Nature communications · 2019Article
- Evolutionary model for the unequal segregation of high copy plasmids.PLoS computational biology · 2019Article
- Segregational Drift and the Interplay between Plasmid Copy Number and Evolvability.Molecular biology and evolution · 2019Article
- Engineered microbial biofuel production and recovery under supercritical carbon dioxide.Nature communications · 2019Article
- Influence of global gene regulatory networks on single cell heterogeneity of green fluorescent protein production in Bacillus subtilis.Microbial cell factories · 2018Article
- Rapid acquisition and model-based analysis of cell-free transcription-translation reactions from nonmodel bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Copy number variability of expression plasmids determined by cell sorting and Droplet Digital PCR.Microbial cell factories · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the past 2 decades, Bacillus megaterium has been systematically developed for the gram-per-liter scale production of recombinant proteins. The plasmid-based expression systems employed use a xylose-controlled promoter. Protein production analyses at the single-cell level using green fluorescent protein as a model product revealed cell culture heterogeneity characterized by a significant proportion of less productive bacteria. Due to the enormous size of B. megaterium, such bistable behavior seen in subpopulations was readily analyzed by time lapse microscopy and flow cytometry. Cell culture heterogeneity was not caused simply by plasmid loss: instead, an asymmetric distribution of plasmids during cell division was detected during the exponential-growth phase. Multicopy plasmids are generally randomly distributed between daughter cells. However, in vivo and in vitro experiments demonstrated that under conditions of strong protein production, plasmids are retained at one of the cell poles. Furthermore, it was found that cells with accumulated plasmids and high protein production ceased cell division. As a consequence, the overall protein production of the culture was achieved mainly by the subpopulation with a sufficient plasmid copy number. Based on our experimental data, we propose a model whereby the distribution of multicopy plasmids is controlled by polar fixation under protein production conditions. Thereby, cell lines with fluctuating plasmid abundance arise, which results in population heterogeneity. Our results provide initial insights into the mechanism of cellular heterogeneity during plasmid-based recombinant protein production in a Bacillus species.
Indexed as
Identifiers
What OpenQuestion holds
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.