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Review
. 2025 Jun 16;23(6):255.
doi: 10.3390/md23060255.

Bioactive Polyketides from Amphidinium spp.: An In-Depth Review of Biosynthesis, Applications, and Current Research Trends

Noemi Russo  1 , Giulia Quaini  1   2 , Marcello Ziaco  2 , Daniela Castiglia  2 , Alessandra Ruggiero  3 , Vincenzo D'Amelia  4 , Concetta Di Napoli  1 , Sergio Esposito  1 , Angelo Fontana  1   2 , Genoveffa Nuzzo  2 , Simone Landi  1
Affiliations
Review

Bioactive Polyketides from Amphidinium spp.: An In-Depth Review of Biosynthesis, Applications, and Current Research Trends

Noemi Russo et al. Mar Drugs. .

Abstract

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 Amphidinium 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 Amphidinium-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.

Keywords: Amphidinium spp.; dinoflagellates; marine natural products; polyketide synthases; polyketides.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Map of countries (A) and number of isolated Amphidinium species (B) (Amphidinium carterae, Amphidinium cupulatisquana, Amphidinium fijiensis, Amphidinium gibbosum, Amphidinium herdmanii, Amphidinium incoloratum, Amphidinium magnum, Amphidinium massartii, Amphidinium cf. massartii, Amphidinium mootonorum, Amphidinium operculatum, Amphidinium pseudomassartii, Amphidinium paucianulatum, Amphidinium steinii, Amphidinium theodori, Amphidinium thermaeum, Amphidinium cf. thermeaum, Amphidinium trulla, Amphidinium tomasii). This figure includes 211 different strains collected from all over the world.
Figure 2
Figure 2
Amphidinins A (1), G, (2), C (3), D (4), E (5), F (6), B (7), amphirionin 2 (8).
Figure 3
Figure 3
Amphidinols A (9), B (10), C (11), 2 (12), 3 (13), 9 (14), 11 (15), 13 (16), 14 (17), 15 (18), 7 (19), 17 (20), 18 (21), 19 (22), 20 (23), 21 (24).
Figure 4
Figure 4
Luteophanol A (25), Lingshuiol A (26), Colopsinol A (27), C (28), E (29), Amdigenol A (30), E (31), G (32), Amphezonol A (33), Carteraol E (34), Karatungiol A (35), B (36).
Figure 5
Figure 5
Amphidinolide Q (37), A (38), B (39), B1 (40), T2 (41), U (42), W (43), X (44), Y (45), C (46), Caribenolide I (47), Amphidinolactone A (48), Iriomoteolide 1a (49), 2a (50), 3a (51), 3b (52), 11a (53), 13a (54), 14a (55), 14b (56), Amphidinolide O (57), and P (58).
Figure 6
Figure 6
Putative biosynthesis of the initial segment of Amphidinol 3: a schematic representation of the polyhydroxy moiety elongation based on modular type I PKS. Domains are acyl transferase (AT), acyl carrier protein (ACP), ketosynthase (KS), ketoreductase (KR), and dehydratase (DH).
Figure 7
Figure 7
Acetate labelling pattern of amphidinolides J (1), H (2), G (3), B (4), C (5), W (6), T1 (7), X (8), Y (9), and P (10).
Figure 8
Figure 8
Acetate labelling pattern of amphidinol 4 (1), 2 (2), 17 (3), A (4), amphirionine-4 (5), and amphidinin A (6).
Figure 9
Figure 9
Timeline diagram of the most relevant discoveries concerning Amphidinium spp.
See this image and copyright information in PMC

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