Optimization of Light and Nutrients Supply to Stabilize Long-Term Industrial Cultivation of Metabolically Engineered Cyanobacteria: A Model-Based Analysis
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High Resolution Image Download MS PowerPoint Slide Metabolically engineered cyanobacteria are promising photosynthetic cell factories to produce valuable compounds in view of a bio-based industry. However, when the producer population is affected by a production burden, it usually experiences genetic instability leading to cells that lose the production capability, here defined as retro-mutants, which in the long-term take over the culture. Here we show that by exploitation of differences in nutrient and light use between these two phenotypes, in a continuous culture the operative conditions can be set to specifically select the producers. A mathematical model-based analysis used to investigate the effect of kinetic parameters shows that in specific combinations of their values, a continuous stirred-tank reactor (CSTR) can be operated to favor the producer’s growth. The feasibility of the approach proposed is discussed in the context of literature data. On the basis of overall mass and energy balance analysis, a new approach to stabilize the producer phenotype in long-term industrial cultivation is proposed.
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Long-term studies have shown that production burden can favour the emergence of non-producing or low-producing cells during extended cultivation.
“Long-term studies have also shown that production burden can favour the emergence of non-producing or low-producing cells during extended cultivation, emphasising the need to evaluate stability over many generations rather than relying only on early-stage titres [201].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [201]
The Introduction (pp. 1–2) says production burden gives cells that lose production a selective advantage and reports that retro-mutants can take over after a number of generations. That supports the central point, but this source is a model-based analysis, not itself a long-term cultivation study; the cited passages do not establish the emergence of low-producing cells or compare long-term stability with early-stage titres. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSuch genetic instability may result in the gradual loss of engineered traits and diminished production yields over time.
“Such genetic instability may result in the gradual loss of engineered traits and diminished production yields over time [201].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [201]
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“Such genetic instability may result in the gradual loss of engineered traits and diminished production yields over time [201].”
- Authors
- Battaglino, B., Arduino, A., Pagliano, C., Sforza, E., & Bertucco, A.
- Affiliations
- Politecnico di Torino (IT)
- Istituto Nazionale di Ricerca Metrologica (IT)
- University of Padua (IT)
- Corresponding author
- Sforza, Eleonora
- Venue
- Industrial & Engineering Chemistry Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-02-09
- Volume
- 60
- Issue
- 29
- Pages
- 10455-10465
- ISSN
- 0888-5885 (ISSN-L)
- 1520-5045
- OpenAlex
- W3126402745
- Cited by
- 8
- References
- 63
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2021: 1
- FWCI
- 0.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Industrial & Engineering Chemistry Research (publishedVersion, cc-by)
- CINECA IRIS Institutional Research Information System (IRIS Istituto Nazionale di Ricerca Metrologica) (submittedVersion, other-oa)
- PORTO@Iris (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (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
- Physical Sciences › Engineering › Biomedical Engineering › Fluid Dynamics and Mixing
- Keywords
- genomic instability, continuous stirred tank reactor, light supply, nutrient supply, continuous culture, kinetic parameters, mass and energy balance, bioproduction
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