Aetokthonotoxin
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. 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. 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. The total synthesis of AETX has been achieved in 2021, the enzymatic functions of the 5 enzymes involved in AETX biosynthesis were described in 2022. Biosynthesis

The biosynthesis of AETX and the functions of the enzymes AetA, AetB, AetD, AetE, and AetF were described in 2022. 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. See also
Cyanotoxin

References

Neurotoxins
Cyanotoxins
Bacterial alkaloids
Nitriles
Bromoarenes
Indoles
Bromine-containing natural products