Vacuolar myelinopathy is a fatal neurological disease that was initially discovered during a mysterious mass mortality of bald eagles in Arkansas in the United States. The cause of this wildlife disease has eluded scientists for decades while its occurrence has continued to spread throughout freshwater reservoirs in the southeastern United States. Recent studies have demonstrated that vacuolar myelinopathy is induced by consumption of the epiphytic cyanobacterial species growing on aquatic vegetation, primarily the invasive Here, we describe the identification, biosynthetic gene cluster, and biological activity of aetokthonotoxin, a pentabrominated biindole alkaloid that is produced by the cyanobacterium We identify this cyanobacterial neurotoxin as the causal agent of vacuolar myelinopathy and discuss environmental factors-especially bromide availability-that promote toxin production.
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http://dx.doi.org/10.1126/science.aax9050 | DOI Listing |
J Phycol
December 2024
Faculty of Science, Department of Botany, University of South Bohemia, České Budějovice, Czech Republic.
Over 400 cyanobacterial genera have been described up to the present. Since the Cambridge Rules (https://www.iapt-taxon.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2023
Institute of Pharmacy, Pharmacognosy, Martin-Luther-University Halle-Wittenberg, Halle (Saale) 06120, Germany.
Cyanobacteria are infamous producers of toxins. While the toxic potential of planktonic cyanobacterial blooms is well documented, the ecosystem level effects of toxigenic benthic and epiphytic cyanobacteria are an understudied threat. The freshwater epiphytic cyanobacterium has recently been shown to produce the "eagle killer" neurotoxin aetokthonotoxin (AETX) causing the fatal neurological disease vacuolar myelinopathy.
View Article and Find Full Text PDFHarmful Algae
June 2023
Biology Centre of the CAS, Institute of Hydrobiology, České Budějovice, 370 05 Czechia; University of South Bohemia, Faculty of Science, České Budějovice, 370 05 Czechia; Centre Algatech, Institute of Microbiology of the CAS, Třeboň, 379 01 Czechia. Electronic address:
Cyanobacteria are well known producers of bioactive metabolites, including harmful substances. The recently discovered "eagle killer" neurotoxin aetokthonotoxin (AETX) is produced by the epiphytic cyanobacterium Aetokthonos hydrillicola growing on invasive water thyme (Hydrilla verticillata). The biosynthetic gene cluster of AETX was previously identified from an Aetokthonos strain isolated from the J.
View Article and Find Full Text PDFJ Am Chem Soc
February 2022
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093, United States.
Aetokthonotoxin (AETX) is a cyanobacterial neurotoxin that causes vacuolar myelinopathy, a neurological disease that is particularly deadly to bald eagles in the United States. The recently characterized AETX is structurally unique among cyanotoxins and is composed of a pentabrominated biindole nitrile. Herein we report the discovery of an efficient, five-enzyme biosynthetic pathway that the freshwater cyanobacterium uses to convert two molecules of tryptophan to AETX.
View Article and Find Full Text PDFChemistry
August 2021
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle/Saale, Germany.
Aetokthonotoxin has recently been identified as the cyanobacterial neurotoxin causing Vacuolar Myelinopathy, a fatal neurologic disease, spreading through a trophic cascade and affecting birds of prey such as the bald eagle in the USA. Here, we describe the total synthesis of this specialized metabolite. The complex, highly brominated 1,2'-biindole could be synthesized via a Somei-type Michael reaction as key step.
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