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Tailoring regulatory components for metabolic engineering in cyanobacteria
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Abstract The looming climate crisis has prompted an ever‐growing interest in cyanobacteria due to their potential as sustainable production platforms for the synthesis of energy carriers and value‐added chemicals from CO2 and sunlight. Nonetheless, cyanobacteria are yet to compete with heterotrophic systems in terms of space‐time yields and consequently production costs. One major drawback leading to the low production performance observed in cyanobacteria is the limited ability to utilize the full capacity of the photosynthetic apparatus and its associated systems, i.e. CO2 fixation and the directly connected metabolism. In this review, novel insights into various levels of metabolic regulation of cyanobacteria are discussed, including the potential of targeting these regulatory mechanisms to create a chassis with a phenotype favorable for photoautotrophic production. Compared to conventional metabolic engineering approaches, minor perturbations of regulatory mechanisms can have wide‐ranging effects.
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Overexpression or poorly coordinated expression can impose metabolic burdens, lead to the accumulation of toxic intermediates, deplete cofactors, and reduce host viability.
“Overexpression or poorly coordinated expression can impose metabolic burdens, lead to the accumulation of toxic intermediates, deplete cofactors, and reduce host viability [213].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [213]
The Abstract (page unavailable) links pathway overexpression to metabolic burden and identifies potentially toxic intermediates; it also reports reduced growth in an engineered strain. Section 3.2 describes a condition-specific lethal overexpression example. Section 4.2 says NADPH availability may limit production, but does not establish that overexpression depletes cofactors, so that part of the claim is not supported. (LLM, conf=0.84)
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From Photosynthesis to Industrial Applications
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“Overexpression or poorly coordinated expression can impose metabolic burdens, lead to the accumulation of toxic intermediates, deplete cofactors, and reduce host viability [213].”
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Self-citationBecker, N. S., Hufnagel, F., Bolay, P., Otec, K., Orthwein, T., Kulik, A., Fink, P., Lenz, C., Lindberg, P., Forchhammer, K., et al. (2026) · Microbial Cell Factories · doi:10.1186/s12934-026-03033-7 · Cited by 1
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Epigenetic control of tetrapyrrole biosynthesis by m4 C DNA methylation in a cyanobacteriumPreprint
Schmidt, N., Stappert, N., Nimura-Matsune, K., Watanabe, S., Sobotka, R., Hagemann, M., & Hess, W. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.20.608618
Engineering primary metabolism for sustainable production of isoprene in Synechocystis sp. PCC 6803
Bolay, P., Janssen, K. N., Timm, S., Hagemann, M., & Lindberg, P. (2026) · Microbial Cell Factories · doi:10.1186/s12934-026-03040-8
Self-citation
Metadata
- Authors
- Bolay, P., Dodge, N., Janssen, K., Jensen, P. E., & Lindberg, P.
- Affiliations
- Uppsala University (SE)
- University of Copenhagen (DK)
- Corresponding author
- Lindberg, Pia
- Venue
- Physiologia Plantarum
- Publisher
- Wiley
- Published
- 2024-04-30
- Volume
- 176
- Issue
- 3
- Pages
- e14316-e14316
- ISSN
- 0031-9317 (ISSN-L)
- 1399-3054
- OpenAlex
- W4396519478
- Cited by
- 13
- References
- 147
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Physiologia Plantarum (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Funders
- Carl Tryggers Stiftelse för Vetenskaplig Forskning (18‐224)
- Novo Nordisk Fonden (NNF19OC0057634)
- Energimyndigheten (38334‐3)
- 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 › Photosynthetic Processes and Mechanisms
- Keywords
- cyanobacteria, metabolic engineering, metabolic regulation, regulatory component, CO2 fixation, photosynthetic apparatus, chassis organisms, space-time yield, value-added chemicals
- MeSH terms
- Cyanobacteria, Carbon Dioxide, Photosynthesis, Metabolic Engineering
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