Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4
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Abstract
Cyanobacteria are prolific producers of natural products, and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters, and here we present the use of Anabaena sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native Anabaena 7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by coconjugation.
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Codon-optimised genes enabled production of lyngbyatoxin A, pendolmycin and teleocidin B-4 in Anabaena sp. PCC 7120, demonstrating that cyanobacteria can support more complex natural product biosynthesis beyond simple linear pathways.
“This system was subsequently expanded as a combinatorial platform for related indolactam natural products, where codon-optimised genes enabled the production of lyngbyatoxin A, pendolmycin and teleocidin B-4 in Anabaena sp. PCC 7120, demonstrating that cyanobacteria can support more complex natural product biosynthesis beyond simple linear pathways [183].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [183]
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- Authors
- Videau, P., Wells, K. N., Singh, A. J., Eiting, J., Proteau, P. J., & Philmus, B.
- Affiliations
- Oregon State University (US)
- Corresponding author
- Philmus, Benjamin
- Venue
- ACS Synthetic Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-12-17
- Volume
- 9
- Issue
- 1
- Pages
- 63-75
- ISSN
- 2161-5063 (ISSN-L)
- PMC
- PMC7384983
- OpenAlex
- W2995487546
- Cited by
- 27
- References
- 41
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 4
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- ACS Synthetic Biology (publishedVersion)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by-nc-nd)
- Funders
- M.J. Murdock Charitable Trust (2014162)
- Office of the Director (S10OD018518)
- BP
- National Institute of General Medical Sciences (1R15GM117541)
- College of Pharmacy, Oregon State University
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Anabaena sp. PCC 7120, cyanobacterial natural products, heterologous expression, lyngbyatoxin A, combinatorial biosynthesis, codon optimization, two-plasmid system
- MeSH terms
- Alkaloids, Bacterial Proteins, Biological Products, Codon, Genes, Bacterial, Multigene Family, Lyngbya Toxins, Plasmids, Anabaena, Metabolic Engineering
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