Anatoxin-a(S) – the currently only naturally occurring organophosphate we know of

Fig. 1: Dolichospermum sp. (formerly classified as Anabaena sp.) (left) can form toxic cyanobacterial blooms (right).

Anatoxin-a(S) is a unique cyanotoxin as it currently is the only naturally occurring organophosphate we know of. Despite its similar name, mode of action and producing cyanobacteria, it has a clearly distinguishable structure compared to another neurotoxic cyanotoxin anatoxin-a. It has been detected in Anabaena strains (now classified as a new genera Dolichospermum), and can co-occur with hepatotoxic microcystins. The neurotoxin has been identified in countries in Northern and Southern America, Europe and in the Arabian Peninsula.

Fig. 2: Structure of anatoxin-a(S).

Anatoxin-a(S) is a phosphorylated cyclic N-hydroxyguanidine irreversibly inhibiting peripheral acetylcholine esterases, resulting in the blockage of nerve fluxes similar to insecticide paraoxon, drug pyridostigmine or chemical warfare agent sarin.

Intoxication with anatoxin-a(S) has been reported for birds, dogs, or swine with symptoms in mammals including hypersalivation, lacrimation, fasciculation, urinary incontinence, convulsions, death due to respiratory arrest. Toxicological examinations showed lethality in mice and rats with LD₅₀ ranging 20 - 40 μg/kg within 30 min after i.p. injection. The cholinesterase inhibitive effect has also been shown in fish and crustaceans. Earlier studies suggested dosing of atropine in combination with activated charcoal or other cholinergic blockers for the treatment of anatoxin-a(S) related poisoning.

Anatoxin-a(S) has a polar character and thus is not expected to cross the blood-brain barrier. The alkaloid is fairly unstable, readily decomposing at temperatures > 40 ℃ and under alkaline conditions.

SMILES: CN(C)C[C@H]1CN=C(N1OP(=O)(O)OC)N

References:

• Beasley VR, Cook WO, Dahlem AM, Hooser SB, Lovell RA, Valentine WM. 1989. Algae intoxication in livestock and waterfowl. Vet Clin North Am Food Anim Pract 5:345-361. doi: 10.1016/S0749-0720(15)30980-4.
• Matsunaga S, Moore RE, Niemczura WP. 1989. Anatoxin-a(S), a Potent Anticholinesterase from Anabaena flos-aquae. J Am Chem Soc 111:8021-8023. doi: 10.1021/ja00202a057.
• Metcalf JS, Bruno M. 2016. Anatoxin-a(S). In: Handbook of Cyanobacterial Monitoring and Cyanotoxin Analysis. John Wiley & Sons, Ltd, pp 155-159. doi: 10.1002/9781119068761.ch15.

Pictures:

• Microscopic picture of Anabaena sp.: https://de.wikipedia.org/wiki/Anabaena#/media/File:Anabaena_sp.jpeg (last accessed: 11/04/2018)
• Cyanobacterial bloom: http://www.apms.org/wp/wp-content/uploads/2014/07/ana_mic.jpg (last accessed: 11/04/2018)