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
ChemSpider
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-killer 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 ions in freshwater systems and requires an interplay between the toxin-producing cyanobacterium Aetokthonos hydrillicola and the host plant it requires to live ( Hydrilla verticillata ), 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 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]

Contents

Biosynthesis

The enzymatic pathway used to assemble AETX from tryptophan Aetokthonotoxin svg 1.svg
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.jpg
Toxin transmission from cyanobacteria to the bald eagle

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.
  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. 1 2 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.
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