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Neurotoxic Alkaloids from Cyanobacteria

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Abstract

Cyanobacteria produce a wealth of secondary metabolites that are very diverse in chemical structure and in biological activity. A number of neurotoxins have been identified in strains of cyanobacteria including anatoxin-a and its higher homologue homoanatoxin-a, anatoxin-a(S), saxitoxins, and related paralytic shellfish toxins. This chapter focuses on these neurotoxic alkaloids from cyanobacteria, with emphasis on the chemical, biochemical, toxicological, and biosynthetic aspects. Anatoxin-a and homoanatoxin-a are two deadly potent agonists of the nicotinic acetylcholine receptor at the neuromuscular junction, provoking the rapid death of animals after respiratory failure. The chemistry and the pharmacology of these neurotoxins have been well studied, while their biosynthesis was recently deciphered. Our knowledge concerning anatoxin-a(S), an irreversible inhibitor of acetylcholine esterase, lies far behind and future work will be needed. Saxitoxin and its analogues, the paralytic shellfish toxins, have been associated with massive intoxication episodes in marine environment. They act as blockers of voltage-gated sodium channels provoking death in animals at low doses. The chemistry, pharmacology, and biosynthesis of saxitoxins have been well described. The genetic origin of the biosynthetic genes of this ancient toxin has been studied by detailed phylogenetic analysis.

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Abbreviations

ACP:

Acyl carrier protein

AOP:

Advance oxidation process

AT:

Acyltransferase

ATX:

Anatoxin-a

CM:

Methyltransferase

Cy:

Cyclase

DH:

Dehydratase

ER:

Enoyl reductase

GC-MS:

Gas chromatography coupled to mass spectrometry

HATX:

Homoanatoxin-a

HPLC:

High pressure liquid chromatography

i.p.:

Intraperitoneal

KR:

Keto reductase

KS:

Ketosynthase

LC-FLD:

Liquid chromatography coupled to a fluorescence detector

LC-MS2 :

Liquid chromatography coupled to tandem mass spectrometry

LC-UV:

Liquid chromatography coupled to a UV detector

LD:

Lethal dose

nAChR:

nicotinic acetylcholine receptor

PKS:

Polyketide synthase

PSP:

Paralytic shellfish poisoning

PST:

Paralytic shellfish toxin

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Authors and Affiliations

  1. Hormone Laboratory, Haukeland University Hospital, Bergen, 5021, Norway

    Dr. Ralf Kellmann

  2. Laboratoire Charles Friedel, Chimie ParisTech, ENSCP, CNRS, UMR 7223, 11 rue Pierre et Marie Curie, Paris, 75231, France

    Olivier Ploux

  3. School of Biotechnology and Biomolecular Sciences and Australian Centre for Astrobiology, University of New South Wales, Sydney, NSW, 2052, Australia

    Dr. Brett A. Neilan

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    Kishan Gopal Ramawat

  2. Institute of Vine and Wine Sciences, Biological-Active Plant Substances Study, University of Bordeaux, 210 Chemin de Leysotte CS 50008, Villenave d'Ornon, 33882, France

    Jean-Michel Mérillon

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Kellmann, R., Ploux, O., Neilan, B.A. (2013). Neurotoxic Alkaloids from Cyanobacteria. In: Ramawat, K., Mérillon, JM. (eds) Natural Products. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22144-6_47

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