Assessing and reducing phenotypic instability in cyanobacteria
Open accessAbstract
Cyanobacteria have promising potential as sustainable cell factories. However, one challenge that is still largely unreported in scaling-up cyanobacteria bioproduction is phenotypic instability, where the emergence and selection of nonproducing cells leading to loss in production has longer evolutionary timescales to take place in industrial-scale bioreactors. Quantifying phenotypic instability early on in strain development allows researchers to make informed decisions on whether to proceed with scalable designs, or if present, devise countermeasures to reduce instability. One particularly effective strategy to mitigate instability is the use of genome-scale metabolic models to design growth-coupled production strains. In silico studies have predicted that creating certain cofactor imbalances or removing recycling reactions in cyanobacteria can be exploited to stably produce a wide variety of metabolites.
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Non-producing cells may emerge and become enriched during scale-up or prolonged cultivation.
“Consequently, future efforts should prioritise pathway designs that are both productive and stable over extended cultivation periods, particularly because non-producing cells may emerge and become enriched during scale-up or prolonged cultivation [217].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [217]
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“Additionally, evaluating pathway stability over prolonged cultivation, rather than relying solely on short-term product yields, will be important [217].”
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- Authors
- Guillaume, M. C., & Branco dos Santos, F.
- Affiliations
- University of Amsterdam (NL)
- Venue
- Current Opinion in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 80
- Pages
- 102899
- ISSN
- 0958-1669 (ISSN-L)
- OpenAlex
- W4318486314
- Cited by
- 11
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Biotechnology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Algal biology and biofuel production
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- phenotypic instability, cyanobacteria, cell factories, genome-scale metabolic models, cofactor recycling, strain design
- MeSH terms
- Cyanobacteria, Biological Evolution, Bioreactors, Metabolic Engineering
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