Aetokthonotoxin

Last updated
Aetokthonotoxin
Aetokthonotoxin.png
Names
IUPAC name
5,7-Dibromo-2-(2,3,5-tribromoindol-1-yl)-1H-indole-3-carbonitrile
Identifiers
3D model (JSmol)
ChEBI
PubChem CID
  • InChI=1S/C17H6Br5N3/c18-7-1-2-13-10(3-7)14(21)16(22)25(13)17-11(6-23)9-4-8(19)5-12(20)15(9)24-17/h1-5,24H
    Key: JXJDQKCOJBAPQM-UHFFFAOYSA-N
  • C1=CC2=C(C=C1Br)C(=C(N2C3=C(C4=C(N3)C(=CC(=C4)Br)Br)C#N)Br)Br
Properties
C17H6Br5N3
Molar mass 651.776 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Aetokthonotoxin (AETX), colloquially known as eagle toxin, is a chemical compound that was identified in 2021 as the cyanobacterial neurotoxin causing vacuolar myelinopathy (VM) in eagles in North America. [1] As the biosynthesis of aetokthonotoxin depends on the availability of bromide in freshwater systems and requires an interplay between the toxin-producing cyanobacterium Aetokthonos hydrillicola and the host plant it epiphytically grows on (most importantly hydrilla), it took more than 25 years to identify aetokthonotoxin as the VM-inducing toxin after the disease has first been diagnosed in bald eagles in 1994. [2] The toxin cascades through the food-chain: Among other animals, it affects fish and waterfowl such as coots or ducks which feed on hydrilla colonized with the cyanobacterium. Aetokthonotoxin is transmitted to raptors, such as the bald eagle, that prey on these affected animals. [3] The total synthesis of AETX has been achieved in 2021, [4] the enzymatic functions of the 5 enzymes involved in AETX biosynthesis were described in 2022. [5]

Contents

Biosynthesis

The enzymes and starting materials used to assemble AETX Aetokthonotoxin svg 1.svg
The enzymes and starting materials used to assemble AETX

The biosynthesis of AETX and the functions of the enzymes AetA, AetB, AetD, AetE, and AetF were described in 2022. [5] AetF, a FAD-dependent halogenase, brominates L-tryptophan at the C5 position. The 5-bromo-L-tryptophan can then undergo two separate reactions. One route involves a second bromination by AetF at C7 to yield 5,7-dibromo-L-tryptophan. This molecule then goes on to react with AetD, an iron-dependent nitrile synthase, to form dibromo-indole-3-carbonitrile. The second route for 5-bromo-L-tryptophan involves the tryptophanase AetE, which converts the 5-bromo-L-tryptophan into 5-bromoindole. 5-bromoindole can then go on to react with a different FAD-dependent halogenase AetA to form 2,3,5-tribromoindole. 2,3,5-tribromoindole and dibromo-indole-3-carbonitrile then undergo biaryl coupling facilitated by the cytochrome P-450 AetB to form AETX.

Toxin transmission from cyanobacteria to the bald eagle Toxin transmission from cyanobacteria to the bald eagle.jpg
Toxin transmission from cyanobacteria to the bald eagle

See also

Related Research Articles

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Cyanotoxins are toxins produced by cyanobacteria. Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such concentrations that they can poison and even kill animals and humans. Cyanotoxins can also accumulate in other animals such as fish and shellfish, and cause poisonings such as shellfish poisoning.

<i>Hydrilla</i> Species of plant

Hydrilla (waterthyme) is a genus of aquatic plant, usually treated as containing just one species, Hydrilla verticillata, though some botanists divide it into several species. It is native to the cool and warm waters of the Old World in Asia, Africa and Australia, with a sparse, scattered distribution; in Australia from Northern Territory, Queensland, and New South Wales.

<span class="mw-page-title-main">Indole-3-acetic acid</span> Chemical compound

Indole-3-acetic acid is the most common naturally occurring plant hormone of the auxin class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists. IAA is a derivative of indole, containing a carboxymethyl substituent. It is a colorless solid that is soluble in polar organic solvents.

<span class="mw-page-title-main">Paralytic shellfish poisoning</span> Syndrome of shellfish poisoning

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<span class="mw-page-title-main">Cyclopiazonic acid</span> Chemical compound

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β-Methylamino-<small>L</small>-alanine Chemical compound

β-Methylamino-L-alanine, or BMAA, is a non-proteinogenic amino acid produced by cyanobacteria. BMAA is a neurotoxin. Its potential role in various neurodegenerative disorders is the subject of scientific research.

<span class="mw-page-title-main">Anatoxin-a</span> Chemical compound

Anatoxin-a, also known as Very Fast Death Factor (VFDF), is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity. It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin is produced by multiple genera of cyanobacteria and has been reported in North America, South America, Central America, Europe, Africa, Asia, and Oceania. Symptoms of anatoxin-a toxicity include loss of coordination, muscular fasciculations, convulsions and death by respiratory paralysis. Its mode of action is through the nicotinic acetylcholine receptor (nAchR) where it mimics the binding of the receptor's natural ligand, acetylcholine. As such, anatoxin-a has been used for medicinal purposes to investigate diseases characterized by low acetylcholine levels. Due to its high toxicity and potential presence in drinking water, anatoxin-a poses a threat to animals, including humans. While methods for detection and water treatment exist, scientists have called for more research to improve reliability and efficacy. Anatoxin-a is not to be confused with guanitoxin, another potent cyanotoxin that has a similar mechanism of action to that of anatoxin-a and is produced by many of the same cyanobacteria genera, but is structurally unrelated.

<span class="mw-page-title-main">Nodularin</span> Chemical compound

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<span class="mw-page-title-main">Paxilline</span> Chemical compound

Paxilline is a toxic, tremorgenic diterpene indole polycyclic alkaloid molecule produced by Penicillium paxilli which was first characterized in 1975. Paxilline is one of a class of tremorigenic mycotoxins, is a potassium channel blocker, and is potentially genotoxic.

<span class="mw-page-title-main">Indolocarbazole</span> Class of chemical compounds

Indolocarbazoles (ICZs) are a class of compounds that are under current study due to their potential as anti-cancer drugs and the prospective number of derivatives and uses found from the basic backbone alone. First isolated in 1977, a wide range of structures and derivatives have been found or developed throughout the world. Due to the extensive number of structures available, this review will focus on the more important groups here while covering their occurrence, biological activity, biosynthesis, and laboratory synthesis.

<span class="mw-page-title-main">Lyngbyatoxin-a</span> Chemical compound

Lyngbyatoxin-a is a cyanotoxin produced by certain cyanobacteria species, most notably Moorea producens. It is produced as defense mechanism to ward off any would-be predators of the bacterium, being a potent blister agent as well as carcinogen. Low concentrations cause a common skin condition known as seaweed dermatitis.

<span class="mw-page-title-main">Scytonemin</span> Chemical compound

Scytonemin is a secondary metabolite and an extracellular matrix (sheath) pigment synthesized by many strains of cyanobacteria, including Nostoc, Scytonema, Calothrix, Lyngbya, Rivularia, Chlorogloeopsis, and Hyella. Scytonemin-synthesizing cyanobacteria often inhabit highly insolated terrestrial, freshwater and coastal environments such as deserts, semideserts, rocks, cliffs, marine intertidal flats, and hot springs.

<i>Microcystis aeruginosa</i> Species of bacterium

Microcystis aeruginosa is a species of freshwater cyanobacteria that can form harmful algal blooms of economic and ecological importance. They are the most common toxic cyanobacterial bloom in eutrophic fresh water. Cyanobacteria produce neurotoxins and peptide hepatotoxins, such as microcystin and cyanopeptolin. Microcystis aeruginosa produces numerous congeners of microcystin, with microcystin-LR being the most common. Microcystis blooms have been reported in at least 108 countries, with the production of microcystin noted in at least 79.

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<span class="mw-page-title-main">Tryptophan 7-halogenase</span>

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L-tryptophan—pyruvate aminotransferase is an enzyme with systematic name L-tryptophan:pyruvate aminotransferase. This enzyme catalyses the following chemical reaction

Avian vacuolar myelinopathy (AVM) is a fatal neurological disease that affects various waterbirds and raptors. It is most common in the bald eagle and American coot, and it is known in the killdeer, bufflehead, northern shoveler, American wigeon, Canada goose, great horned owl, mallard, and ring-necked duck. Avian vacuolar myelinopathy is a newly discovered disease that was first identified in the field in 1994 when dead bald eagles were found near DeGray Lake in Arkansas in the United States. Since then, it has spread to four more states and infested multiple aquatic systems including 10 reservoirs. The cause of death is lesions on the brain and spinal cord. A neurotoxin called aetokthonotoxin produced by cyanobacteria causes the disease.

Cyanopeptolins (CPs) are a class of oligopeptides produced by Microcystis and Planktothrix algae strains, and can be neurotoxic. The production of cyanopeptolins occurs through nonribosomal peptides synthases (NRPS).

<span class="mw-page-title-main">Lolitrem B</span> Chemical compound

Lolitrem B is one of many toxins produced by a fungus called Epichloë festucae var. lolii), which grows in Lolium perenne. The fungus is symbiotic with the ryegrass; it doesn't harm the plant, and the toxins it produces kill insects that feed on ryegrass. Lolitrem B is one of these toxins, but it is also harmful to mammals. The shoots and flowers of infected ryegrass have especially high concentrations of lolitrem B, and when livestock eat too much of them, they get perennial ryegrass staggers. At low doses the animals have tremors, and at higher doses they stagger, and at higher yet doses the animals become paralyzed and die. The blood pressure of the animals also goes up. The effect of the lolitrem B comes on slowly and fades out slowly, as it is stored in fat after the ryegrass is eaten. The condition is especially common in New Zealand and Australia, and plant breeders there have been trying to develop strains of fungus that produce toxins only harmful to pests, and not to mammals.

<span class="mw-page-title-main">Indoxyl sulfate</span> Chemical compound

Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary L-tryptophan that acts as a cardiotoxin and uremic toxin. High concentrations of indoxyl sulfate in blood plasma are known to be associated with the development and progression of chronic kidney disease and vascular disease in humans. As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis.

References

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