Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates
Abstract
:1. Introduction
2. Characterization of Main Dinoflagellate Bioactive (Potential) Applications
2.1. Saxitoxin (and Analogues)
2.2. Tetrodotoxin
2.3. Okadaic Acid and Dinophysistoxin
2.4. Yessotoxin
2.5. Pectenotoxin
2.6. Ciguatoxin
2.7. Maitotoxin
2.8. Palytoxin and Ostreocin
2.9. Gambierol
2.10. Brevetoxin
2.11. Azaspiracid
2.12. Gymnocin
2.13. Karlotoxin
2.14. Cyclic Imine Toxins (Spirolide and Gymonodimine)
2.15. Gambieric Acid (Bioactive)
2.16. Goniodomin A (Bioactive)
2.17. Amphidinolide (Bioactive)
2.18. Amphidinol (Bioactive)
3. Biotoxin and Bioactive Production
3.1. Dinoflagellate Bioactive Supply
3.2. Culture of Dinoflagellates and Biotoxin Production
3.2.1. Nutritional Requirements
3.2.2. Culture Light Provision
3.2.3. Bioreactor Culture and Design
4. Final Considerations
Acknowledgments
Conflicts of Interest
References
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---|---|---|---|
10′,11′-modified saxitoxins useful for treatment of pain | Modified saxitoxin | 2017 | US20170029431 |
Use of sodium channel blockers for treatment of neuropathic pain develo** as consequence of chemotherapy | Tetrodotoxin, saxitoxin (analogues and derivatives) | 2017 | US20170000797 |
Ladder-frame polyether conjugates | Brevetoxin, maitotoxin, yessotoxin, gambierol | 2016 | US20160128321 |
Sodium channel blocker for treatment of loss of superficial sensitivity | Gonyautoxin | 2016 | US20160000793 |
Palytoxyn, medical use and process for its isolation | Palytoxin | 2014 | EP3087172 |
Neosaxitoxin combination formulations for prolonged local anesthesia | Neosaxitoxin | 2014 | WO2014145580 |
Treatment of loss of sense of touch with saxitoxin derivatives | Saxitoxin | 2014 | EP2533785 |
Using yessotoxin and its derivatives for treatment of gliomas | Yessotoxin and derivatives | 2013 | ES2393696 |
Use of yessotoxin and analogues and derivatives thereof for treating and/or preventing neurodegenerative diseases linked to tau and beta amyloid | Yessotoxin (analogues and derivatives) | 2013 | US20130035302 |
Use of gambierol for treating and/or preventing neurodegenerative diseases related to tau and beta-amyloid | Gambierol | 2012 | US20120283321 |
Use of yessotoxins and derivatives thereof for treatment and/or prevention of metabolic diseases | Yessotoxin and derivatives | 2012 | WO2012140298 |
Use of gymnodimine, analogues and derivatives for treatment and/or prevention of neurodegenerative diseases associated with tau and beta-amyloid | Gymnodimine (analogues and derivatives) | 2012 | US20120245223 |
Therapeutic use of yessotoxin as human tumor cell growth inhibitor | Yessotoxin | 2011 | EP1875906 |
Methods and compositions for studying, imaging, and treating pain | Saxitoxin, gonyautoxin and other analogues | 2011 | WO2010129864 |
Use of sodium ion channel blocker in treating biology drug resistance of antibiotic | Tetrodotoxin, saxitoxin | 2009 | CN101450056 |
Polyether brevetoxin derivatives as treatment for cystic fibrosis, mucociliary dysfunction, and pulmonary diseases | Brevetoxins and derivatives | 2008 | US7399782 |
Use of sodium channel blockers for treatment of preterm labor | Tetrodotoxin, saxitoxin (analogues and derivatives) | 2007 | WO2007096170 |
Polyether brevetoxin derivatives as treatment for neurotoxic shellfish poisoning and ciguatera fish poisoning | Brevetoxin and derivatives | 2005 | WO2005027903 |
Methods of treating wounds with gonyautoxins | Gonyautoxin | 2005 | WO2005110275 |
Dinoflagellate karlotoxins, methods of isolation and uses thereof | Karlotoxin | 2005 | US2005/0209104 |
Use of yessotoxin in treatment of allergic and asthmatic processes | Yessotoxin | 2003 | EP1875907 |
Toxin | Supplier | Source | Price Range (€ mg−1) |
---|---|---|---|
Okadaic acid | SGA GEN LCL MER SL TC BP SCB | Prorocentrum concavum unkown unkown Prorocentrum sp. unkown unkown unkown Prorocentrum sp. | 1430 3510 561 2538 3479 5000 1210 1850 |
Okadaic acid, ammonium salt | SGA LCL | Prorocentrum concavum unkown | 16,620 561 |
Okadaic acid, sodium salt | SGA GEN LCL SL | Prorocentrum concavum unkown unkown unkown | 9730 2320 561 2657 |
Okadaic acid, potassium salt | SGA GEN LCL | Prorocentrum concavum unkown unkown | 8050 2320 561 |
Okadaic acid, solution | MER | Prorocentrum sp. | 4480 |
Tetrodotoxin | GEN TC | unkown unkown | 451 195 |
Saxitoxin, diacetate | GEN | unkown | 9920 |
Brevetoxin 2 | GEN | unkown | 17,960 |
MER | Karenia brevis | 4390 | |
SCB | Karenia brevis | 5970 | |
Brevetoxin 3 | GEN | unkown | 17,530 |
MER | Karenia brevis | 3880 | |
Brevetoxin 9 | GEN | unkown | 19,380 |
Yessotoxin, antibody | GEN | unkown | 1580 |
Maitotoxin | LCL | unkown | unkown |
Azaspiracid-1 | SCB | Marine mussel | 357,000 |
Azaspiracid-2 | SCB | Marine mussel | 359,000 |
Azaspiracid-3 | SCB | Marine mussel | 540,000 |
Species and Strain | Type of Reactor | Reactor Operation | Reactor Size | Type of Aeration/Agitation | T (°C) | Irradiance Culture System | Light Intensity (µmol m−2 s−1) | Light Regime | Biotoxin Produced | Specific r-Emsarks | Ref. |
---|---|---|---|---|---|---|---|---|---|---|---|
Prorocentrum lima spp. | Carboy | Batch | 36 L | Stirring (discontinuous) | 18 ± 1 | - | 90 ± 5 | Continuous dark/14 h:10 h | Okadaic acid Dinophysistoxin | - | [326] |
Protoceratium reticulatum CAWD129 | Carboy | Batch | 226 L | - | - | - | - | 12 h/12 h | Yessotoxin Furanoyessotoxin | Serial bulk culture (size ~14 L each) | [329] |
Azadinium spinosum 3D9 | Chemostat in series | Continuous | 100 L | Stirring (not specified) | 18 | - | 200 | 16 h/8 h | Azaspiracid | - | [330] |
Azadinium spinosum 3D9 | Tubular PBRs in series | Continuous | 100 L | Stirring (Rushton turbine) | 18 | Neon tube lamps | 200 | 16 h/8 h | Azaspiracid | Culture collected in an aerated harvesting tank (300 L) | [331] |
Alexandrium tamarense ATHK | Airlift PBR | Batch | 2.5 L | Airlift | 22 | Cool-white fluorescent lamps | 60 | Continuous | Saxitoxin | Two-step batch culture method | [332] |
Alexandrium tamarense ATCI01 | Glass rectangular tank | Batch/Semi-continuous | 70 L 40 L | Air bubbling (continuous) | 23 | Cool-white fluorescent lamps | 108 | 16 h/8 h | C2 toxin | - | [333] [334] |
Protoceratium reticulatum GG1AM | Stirred-PBR | Batch/Fed-batch /Semi-continuous | 15 L | Stirring (impeller)/gas sparging | 19 ± 1 | Cool-white fluorescent lamps | 242–766 | - | Yessotoxin | - | [290] |
Protoceratium reticulatum GG1AM and VGO764 | Stirred-glass fermenter | Semi-continuous Fed-batch Continuous | 2 L | Stirring (impeller) | - | Cool-white fluorescent lamps | (e.g., 34, 44, 54, 66, 81, 99, 100) | - | Yessotoxin | - | [335] [270] |
Amphidinium carterae ACRN03 | Airlift bubble column PBR | Semi-continuous | 540 L 320 L 48 L | Compressed air (continuous) | 23.3 ± 2.2 | - | 158 ± 22 (indoor) ~464 (outdoor) | 18 h/ 6h | N/A | Production of biomass | [289] |
Karenia selliformes CAWD79 Alexandrium ostenfeldii CAWD135 Karenia Brevisulcata CAWD82 | Column PBRs Carboy | Batch/ Continuous | 5.4 L 52 L | Magnetic stirring/Air bubbling (low) | - | Cool-white fluorescent lamps | 38 | 12 h/12 h | Gymnodimine Spirolide Brevisulcatic acid | - | [268] |
Karlodinium veneficum K10 | Bubble column PBR | Batch (sequential) | 80 L | Gas Sparging | 21 ± 1 | LEDs | 220 1500 (>7th day) | 12 h/12 h | N/A | - | [287] |
Amphidinium sp. | Flat-bottom flask | Batch | 3 L | - | 25 | - | 108 | 16 h/8 h | Amphidinolide | - | [248] |
Alexandrium minutum AMAD06 and AMAD16 | Alveolar panel PBR | Batch/Semi-continuous | 4 L | Alveoli | - | Cool-white fluorescent lamps | 100 | 12 h/12 h | Gonyautoxin/fraction of saxitoxin, neosaxitoxin and C-toxin | - | [336] |
Alexandrium ostenfeldii CCMP1773 | Flat-bottom vessel | Batch | 8 L | N/A | 16 | Cool-white fluorescent lamps | 155 | 12 h/12 h | Spirolide | - | [337] |
Alexandrium ostenfeldii CCMP1773 | Column PBR | Continuous | 100 L | Stirring (paddle impeller turbines) | 18 | Cool-white fluorescent lamps | 190 | 16 h/8 h | Spirolide | - | [337] |
Alexandrium pacificum HYM9704 | Chemostat system | Batch Semi-continuous | 2 L | Air bubbling | 15 | Cool-white fluorescent lamps | 150 | 12/12 | C-toxin Gonyatoxin Saxitoxin | - | [338] |
Amphidinium carterae (Hulbert) | Plastic cylinder | Batch | 40 L | Airlift | 22 | Cool-white fluorescent lamps | 40 | 12 h/12 h | N/A | Identification of pharmacological activity in vitro using algal extracts | [339] |
Prorocentrum lima CCMP 2579 | Vertical flat PBR | Batch | 100 L | Air bubbling | 20 | Cool-white fluorescent lamps | 100 | 12 h/12 h | Okadaic acid Dinophysistoxins | - | [321] |
Karlodinium veneficum ICMB 252 Alexandrium. minutum AMP4 | Column PBR | Batch (indoors) Semi-continuous (outdoors) | 350 L | Air bubbling | 20 ± 1 (indoors) Variable (outdoors) | Cool-white fluorescent lamps | 110 (indoors) 202–4020 (outdoors) | 12 h/12 h | N/A | Each PBR column size ~35 L each Production of lipids | [340] |
Symbiodinium voratum | Twin Layer PBR (Biofilm-immobilization) | Continuous | 414 cm2 | Air tube (continuous) | 23 ± 1 25 ± 3 | Cool-white fluorescent and Sodium lamps | 26 ± 2 73.5 ± 17.5 | 14 h/10 h | N/A | Production of peridin | [341] |
Amphidinium carterae (JHWAC) Symbiodinium sp. (JHLSD1) Prorocentrum rathymum (JHWPMX1) | Vertical column PBR system (12× column) | Batch | 700 L | Air bubbling | 20 ± 1 | Cool-white fluorescent lamps | 40–50 | 12 h/12 h | N/A | Each PBR column size ~60 L each Screening antioxidant properties | [342] |
Karlodinium veneficum (CCMP 2936) | Vertical column PBR | Batch | 31 L | N/A | 24 | LEDs | 50 | 14 h/10 h | N/A | Study on vertical migration | [343] |
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Assunção, J.; Guedes, A.C.; Malcata, F.X. Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates. Mar. Drugs 2017, 15, 393. https://doi.org/10.3390/md15120393
Assunção J, Guedes AC, Malcata FX. Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates. Marine Drugs. 2017; 15(12):393. https://doi.org/10.3390/md15120393
Chicago/Turabian StyleAssunção, Joana, A. Catarina Guedes, and F. Xavier Malcata. 2017. "Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates" Marine Drugs 15, no. 12: 393. https://doi.org/10.3390/md15120393