Flipping DNA to generate and regulate microbial consortia
Open accessAbstract
Communities of interdependent microbes, found in diverse natural contexts, have recently attracted the attention of bioengineers. Such consortia have potential applications in biosynthesis, with metabolic tasks distributed over several phenotypes, and in live-cell microbicide therapies where phenotypic diversity might aid in immune evasion. Here we investigate one route to generate synthetic microbial consortia and to regulate their phenotypic diversity, through programmed genetic interconversions. In our theoretical model, genotypes involve ordered combinations of DNA elements representing promoters, protein-coding genes, and transcription terminators; genotypic interconversions are driven by a recombinase enzyme that inverts DNA segments; and selectable phenotypes correspond to distinct patterns of gene expression. We analyze the microbial population as it evolves along a graph whose nodes are distinct genotypes and whose edges are interconversions. We show that the steady-state proportion of each genotype depends on its own growth advantage, as well as on its connectivity to other genotypes. Multiple phenotypes with identical or distinct growth rates can be indefinitely maintained in the population, while their proportion can be regulated by varying the rate of DNA flipping. Recombinase-based synthetic constructs have already been implemented; the graph-theoretic framework developed here will be useful in adapting them to generate microbial consortia.
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Cultivating microbes in bioreactors may generate spontaneous mutations, and gene flipping may change their function.
“Moreover, cultivation of microbes in bioreactors may generate spontaneous mutations, and gene flipping may potentially change their function.163”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [163]
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Melanoma and microbiota: Current understanding and future directions
Routy, B., Jackson, T., Mählmann, L., Baumgartner, C. K., Blaser, M., Byrd, A., Corvaia, N., Couts, K., Davar, D., Derosa, L., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2023.12.003 · Cited by 89 · see citing works
- Authors
- Ramadas, R., & Thattai, M.
- Affiliations
- Tata Institute of Fundamental Research (IN)
- Corresponding author
- Thattai, Mukund
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-01
- Volume
- 184
- Issue
- 1
- Pages
- 285-293
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC2800055
- OpenAlex
- W2130462742
- Cited by
- 7
- References
- 46
- Citations by year
- 2023: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- synthetic microbial consortia, recombinases, phenotypic diversity, genotype-phenotype mapping, population evolution, gene expression regulation, microbial communities, biosynthesis
- MeSH terms
- Bacteria, Bacterial Proteins, DNA, Bacterial, Genetic Engineering, Genotype, Models, Genetic, Phenotype, Gene Expression Regulation, Bacterial, Recombinases
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