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Polyketides (PKs) are a widespread class of secondary metabolites with recognised pharmacological properties. These molecules are abundantly produced in the marine environment, especially by dinoflagellate-photosynthetic organisms able to produce several PKs, including neurotoxins, cytotoxins, and immunomodulating agents. The biosynthesis of these compounds is driven by a conserved enzymatic process involving polyketide synthase complexes. Different genera of dinoflagellates produce PKs. Among them, dinoflagellates of the genus are of particular interest due to its ability to produce the following two major families of PKs: amphidinolides and amphidinols. These compounds display remarkable biological activities, including anticancer, antimicrobial, and antifungal effects, making them attractive targets for pharmaceutical research and development. However, the natural yield of -derived polyketides (APKs) is generally low, limiting their potential for sustainable molecular farming. This challenge has prompted interest in developing biotechnological strategies to enhance their production. This review aims to define the current state of studies about APKs, starting from their initial discoveries to the recent understanding of their biosynthetic pathways. Additionally, it summarizes the structures of compounds discovered, highlights their biotechnological potential, and discusses novel trends in their production.
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http://dx.doi.org/10.3390/md23060255 | DOI Listing |
Angew Chem Int Ed Engl
September 2025
Department of Chemical and Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713AV, The Netherlands.
Type III polyketide synthases (T3PKSs) are enzymes that produce diverse compounds of ecological and clinical importance. While well-studied in plants, only a handful of T3PKSs from fungi have been characterised to date. Here, we developed a comprehensive workflow for kingdom-wide characterisation of T3PKSs.
View Article and Find Full Text PDFACS Omega
August 2025
Department of Chemistry, Haverford College, Haverford, Pennsylvania 19041, United States.
The value of microbial natural product pathways extends beyond the chemicals they produce, as the enzymes they encode can be harnessed as biocatalysts. Microbial type II polyketide synthases (PKSs) are particularly noteworthy, as these enzyme assemblies produce complex polyaromatic pharmacophores. Combinatorial biosynthesis with type II PKSs has been described as a promising route for accessing never-before-seen bioactive molecules, but this potential is stymied in part by the lack of functionally compatible noncognate proteins across type II PKS systems.
View Article and Find Full Text PDFInt J Food Microbiol
August 2025
Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi Province 710072, China; National Center of Technology Innovation for Dairy, 8 Guochuang West Road, Chelechao Dairy Development Zone, Tumote Left Banner, Hohhot
Ochratoxin A (OTA), a carcinogenic mycotoxin produced by Aspergillus and Penicillium species that contaminates food crops and threatens public health. Although ergosterol and its synthetic enzymes are important antifungal targets, their regulatory roles and mechanisms in OTA production remain unclear. Therefore, elucidating the roles of ergosterol synthase genes erg3 (C-5 sterol desaturase) and erg24 (C-14 sterol reductase) in oxidative stress response and OTA biosynthesis in Aspergillus carbonarius is of critical importance.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Type II polyketide synthases (PKSs) collectively generate polyketide intermediates of varying chain lengths, which undergo cyclization and further tailoring to produce structurally diverse aromatic polyketides. The length of the polyketide chain is a critical factor shaping the core scaffold of the final product. However, individual type II PKSs typically produce intermediates with a fixed chain length, thereby limiting the structural diversity accessible from a single biosynthetic system.
View Article and Find Full Text PDFAntibiotics (Basel)
July 2025
Department of Pharmacy, Kochi Medical School Hospital, Nankoku-City 783-8505, Japan.
Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies.
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