title: Biosynthesis of anatoxin-a and analogues (anatoxins) in cyanobacteria.
abstract: Freshwater cyanobacteria produce secondary metabolites that are toxic to humans and animals, the so-called cyanotoxins. Among them, anatoxin-a and homoanatoxin-a are potent neurotoxins that are agonists of the nicotinic acetylcholine receptor. These alkaloids provoke a rapid death if ingested at low doses. Recently, the cluster of genes responsible for the biosynthesis of these toxins, the ana cluster, has been identified in Oscillatoria sp. PCC 6506, and a biosynthetic pathway was proposed. This biosynthesis was reconstituted in vitro using purified enzymes confirming the predicted pathway. One of the enzymes, AnaB a prolyl-acyl carrier protein oxidase, was crystallized and its three dimensional structure solved confirming its reaction mechanism. Three other ana clusters have now been identified and sequenced in other cyanobacteria. These clusters show similarities and some differences suggesting a common evolutionary origin. In particular, the cluster from Cylindrospermum stagnale PCC 7417, possesses an extra gene coding for an F420-dependent oxidoreductase that is likely involved in the biosynthesis of dihydroanatoxin-a. This review summarizes all these new data and discusses them in relation to the production of anatoxins in the environment.
authors.affiliation: LIED, UMR 8236 CNRS, Université Paris Diderot, Bâtiment Lamarck B, Boîte courrier 7040, 35 rue Hélène Brion, 75205 Paris Cedex 13, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Méjean
authors.affiliation: LIED, UMR 8236 CNRS, Université Paris Diderot, Bâtiment Lamarck B, Boîte courrier 7040, 35 rue Hélène Brion, 75205 Paris Cedex 13, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paci
authors.affiliation: LIED, UMR 8236 CNRS, Université Paris Diderot, Bâtiment Lamarck B, Boîte courrier 7040, 35 rue Hélène Brion, 75205 Paris Cedex 13, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gautier
authors.affiliation: LIED, UMR 8236 CNRS, Université Paris Diderot, Bâtiment Lamarck B, Boîte courrier 7040, 35 rue Hélène Brion, 75205 Paris Cedex 13, France; Chimie ParisTech, ENSCP, 75005 Paris, France. Electronic address: olivier.ploux@chimie-paristech.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ploux
mesh_terms: D000458:Cyanobacteria / Q000235:genetics / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D005798:Genes, Bacterial; D005810:Multigene Family; D014326:Tropanes / Q000378:metabolism*
chemical_list: D000087522:Cyanobacteria Toxins; D014326:Tropanes; C509783:anatoxin a
keywords: Anatoxin-a; Biosynthesis; Cyanobacteria; Dihydroanatoxin-a; Homoanatoxin-a; Polyketide synthase