User:Alloenzyme/sandbox

Alloenzyme/sandbox
Names
IUPAC name
5,7-Dibromo-2-(2,3,5-tribromoindol-1-yl)-1H-indole-3-carbonitrile
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
  • 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).
Tracking categories (test):

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] It took over 25 years to identify AETX as the VM-inducing toxin due to its synthesis requiring both bromide ions and an interplay between the toxin-producing cyanobacterium Aetokthonos hydrillicola and the host plant it requires to live. [2] The toxin cascades through the food-chain: Among other animals, it builds up in 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, as they prey on AETX poisoned animals.[3] The total synthesis of AETX was achieved in 2021,[4] the enzymatic functions of the 5 enzymes involved in AETX biosynthesis were described in 2022.[5]

Background

In 1994, 29 eagles died in DeGray Lake, Arkansas from unknown causes, closely followed by another 26 in the next two years.[6] These sick eagles displayed extreme difficulty with swimming, flying, perching, and walking. Light microscopy experiments showed that these eagles had cavities in their brains' white matter, otherwise known as avian vacuolar myelinopathy (AVM). At the time, the cause of this AVM was unknown. Researchers first began studying this by taking samples from affected reservoirs and other freshwater sources and feeding it to chickens. However, the chickens did not develop AVM as the eagles had. Researchers then collected additional samples, and using mass spectrometry, detected a novel metabolite that was characterized as Aetokthonos hydrillicola, a cyanobacteria growing on top of the weeds in DeGray Lake. [7] This cyanotoxin was then ingested by the fish species in the area, and subsequently ingested by the eagles. Because eagles were apex predators in DeGray, Arkansas, they suffered from bioaccumulation, and suffered the effects of aetokthonotoxin more severely.

Biosynthesis

The enzymatic pathway used to assemble AETX from tryptophan

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 5 position. The 5-bromo-L-tryptophan can then undergo two separate reactions. One route involves a second bromination by AetF at position 7 to yield 5,7-dibromo-L-tryptophan. This molecule then goes on to react with AetD, an iron-dependent nitrile synthase, to form an indole-3-carbonitrile derivative. The second route taken by the 5-bromo-L-tryptophan starting material involves the tryptophanase AetE, which cleaves 5-bromo-L-tryptophan into 5-bromoindole, pyruvic acid and ammonia. 5-bromoindole can then go on to react with a different FAD-dependent halogenase called AetA to form 2,3,5-tribromoindole. the 2,3,5-tribromoindole and the dibrominated-indole-3-carbonitrile then undergo biaryl coupling facilitated by the cytochrome P450 enzyme AetB to form AETX.

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

Metabolic Pathway

Though the specific metabolic pathway of AETX through the metabolic pathway aren't entirely elucidated yet, it is speculated that AETX and other cyanobacteria can act similarly to dolastatins and other mitotic inhibitors. [8] These mitotic inhibitors have been shown to impact cells' ability to reproduce by binding to tubulin and disrupting the assembly of microtubulin during the cell cycle. Thus, when cells eventually become apoptotic, the affected eagles are unable to grow and develop new cells.

See also

References

  1. ^ Breinlinger, Steffen; Phillips, Tabitha J.; Haram, Brigette N.; Mareš, Jan; Yerena, José A. Martínez; Hrouzek, Pavel; Sobotka, Roman; Henderson, W. Matthew; Schmieder, Peter; Williams, Susan M.; Lauderdale, James D. (2021-03-26). "Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy". Science. 371 (6536): eaax9050. doi:10.1126/science.aax9050. ISSN 0036-8075. PMC 8318203. PMID 33766860.{{cite journal}}: CS1 maint: article number as page number (link)
  2. ^ "Avian vacuolar myelinopathy". USGS National Wildlife Health Center. Archived from the original on 6 October 2014. Retrieved 24 October 2013.
  3. ^ Birrenkott, A. H.; S. B Wilde; J. J. Hains; J. R. Fisher; T. M. Murphy; C. P. Hope; P. G. Parnell; W. W. Bowerman (2004). "Establishing a food-chain link between aquatic plant material and avian vacuolar myelinopathy in mallards (Anas platyrhynchos)". Journal of Wildlife Diseases. 40 (3): 485–492. doi:10.7589/0090-3558-40.3.485. PMID 15465716.
  4. ^ Ricardo, Manuel G.; Schwark, Markus; Llanes, Dayma; Niedermeyer, Timo H. J.; Westermann, Bernhard (2021-06-03), "Total Synthesis of Aetokthonotoxin, the Cyanobacterial Neurotoxin Causing Vacuolar Myelinopathy", Chemistry – A European Journal (in German), vol. 27, no. 47, pp. 12032–12035, doi:10.1002/chem.202101848, PMC 8453946, PMID 34081364
  5. ^ a b Adak, Sanjoy; Lukowski, April L.; Schäfer, Rebecca J. B.; Moore, Bradley S. (2022-02-10). "From Tryptophan to Toxin: Nature's Convergent Biosynthetic Strategy to Aetokthonotoxin". Journal of the American Chemical Society. 144 (7). American Chemical Society (ACS): 2861–2866. doi:10.1021/jacs.1c12778. ISSN 0002-7863. PMC 9004672. PMID 35142504. S2CID 246702060.
  6. ^ Welch, Melanie K (February 5, 2025). "Bald Eagle Mass Death of the 1990s". Encyclopedia of Arkansas. Mayflower, Arkansas: CALS. Retrieved May 6, 2025.
  7. ^ "There's something in the water, and it's killing America'snationalbird". Massive Science. Retrieved 28 April 2025. Cite error: Unknown parameter "sci" in <ref> tag; supported parameters are dir, follow, group, name (see the help page).
  8. ^ Schwark, Martinez, M; Yerena, JA; Rohrborn, K; Hrouzek, P (2023-10-03). "More than just an eagle killer: The freshwater cyanobacterium Aetokthonos hydrillicola produces highly toxic dolastatin derivatives". Proceedings of the National Academy of Sciences of the United States of America. 120 (40). National Academy of Sciences. doi:10.1073/pnas.2219230120.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Content Disclaimer

Informasi ini disarikan dari Wikipedia dan disajikan kembali untuk tujuan edukasi. Konten tersedia di bawah lisensi CC BY-SA 3.0. Kami tidak bertanggung jawab atas ketidakakuratan data yang bersumber dari kontribusi publik tersebut.

  1. The information displayed on this website is sourced in part or in whole from Wikipedia and has been adapted for the purpose of restating it. We strive to provide accurate and relevant information, however:
  2. There is no guarantee of absolute accuracy. Wikipedia is an open, collaborative project that can be edited by anyone, so information is subject to change.
  3. It is not intended to constitute professional advice. The content displayed is for informational and educational purposes only. For important decisions (e.g., medical, legal, or financial), please consult a professional.
  4. Content copyright. Wikipedia is licensed under the Creative Commons Attribution-ShareAlike License (CC BY-SA). This means that content may be reused with appropriate attribution and shared under a similar license.
  5. Responsible use. Any risk arising from the use of information from this website is entirely the responsibility of the user.