Metabolic engineering of Synechocystis sp. PCC 6803 for improved bisabolene production
Open accessAbstract
Terpenoids are a wide class of organic compounds with industrial relevance. The natural ability of cyanobacteria to produce terpenoids via the methylerythritol 4-phosphate (MEP) pathway makes these organisms appealing candidates for the generation of light-driven cell factories for green chemistry. Here we address the improvement of the production of (E)-α-bisabolene, a valuable biofuel feedstock, in Synechocystis sp. PCC 6803 via sequential heterologous expression of bottleneck enzymes of the native pathway. Expression of the bisabolene synthase is sufficient to complete the biosynthetic pathway of bisabolene. Expression of a farnesyl-pyrophosphate synthase from Escherichia coli did not influence production of bisabolene, while enhancement of the MEP pathway via additional overexpression of 1-deoxy-D-xylulose-5-phosphate synthase (DXS) and IPP/DMAPP isomerase (IDI) significantly increased production per cell. However, in the absence of a carbon sink, the overexpression of DXS and IDI leads to significant growth impairment. The final engineered strain reached a volumetric titre of 9 mg L−1 culture of bisabolene after growing for 12 days. When the cultures were grown in a high cell density (HCD) system, we observed an increase in the volumetric titres by one order of magnitude for all producing-strains. The strain with improved MEP pathway presented an increase twice as much as the remaining engineered strains, yielding more than 180 mg L−1 culture after 10 days of cultivation. Furthermore, the overexpression of these two MEP enzymes prevented the previously reported decrease in the bisabolene specific titres when grown in HCD conditions, where primary metabolism is usually favoured. We conclude that fine-tuning of the cyanobacterial terpenoid pathway is crucial for the generation of microbial platforms for terpenoid production on industrial-scale.
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In Synechocystis sp. PCC 6803, overexpression of the MEP pathway enzymes DXS and IDI without a downstream terpenoid synthase caused significant growth impairment, which was relieved only when a carbon sink was present.
“in Synechocystis sp. PCC 6803, overexpression of the MEP pathway enzymes DXS and IDI without a downstream terpenoid synthase caused significant growth impairment, which was relieved only when a carbon sink was present [145].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [145]
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“…accumulate to concentrations that directly impair host growth; in Synechocystis sp. PCC 6803, overexpression of the MEP pathway enzymes DXS and IDI without a downstream terpenoid synthase caused significant growth impairment, which was relieved only when a carbon sink was present [145].”
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- Authors
- Rodrigues, J. S., & Lindberg, P.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Lindberg, Pia
- Venue
- Metabolic Engineering Communications
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 12
- Pages
- e00159
- ISSN
- 2214-0301 (ISSN-L)
- PMC
- PMC7809396
- OpenAlex
- W3117229861
- Cited by
- 80
- References
- 34
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 12 · 2023: 17 · 2022: 22 · 2021: 6
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Metabolic Engineering Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NordForsk
- Energimyndigheten (38334–3)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- 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
- Keywords
- Synechocystis sp. PCC 6803, terpenoid biosynthesis, methylerythritol phosphate pathway, farnesyl diphosphate synthase, 1-deoxy-D-xylulose 5-phosphate synthase, high cell density culture, biofuel feedstock, metabolic engineering
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