[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.

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.

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.