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MBE Advance Access originally published online on July 8, 2008
Molecular Biology and Evolution 2008 25(9):2031-2041; doi:10.1093/molbev/msn150
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Research Articles

Halogenase Genes in Nonribosomal Peptide Synthetase Gene Clusters of Microcystis (Cyanobacteria): Sporadic Distribution and Evolution

Sabrina Cadel-Six*, Catherine Dauga{dagger}, Anne Marie Castets*, Rosmarie Rippka*, Christiane Bouchier{ddagger}, Nicole Tandeau de Marsac* and Martin Welker*,§,1

* Institut Pasteur, Unité des Cyanobactéries; Centre National de la Recherche Scientifique, Unité de Recherche Associée 2172, Paris, France
{dagger} Institut Pasteur, Genopole Ile de France—Plateforme 4, Paris, France
{ddagger} Institut Pasteur, Genopole Ile de France—Plateforme 1, Paris, France
§ Technische Universität Berlin, Institut Chemie, AG Biochemie & Molekulare Biologie, Berlin, Germany

E-mail: ntmarsac{at}pasteur.fr.

Accepted for publication July 3, 2008.

Cyanobacteria of the genus Microcystis are known to produce secondary metabolites of large structural diversity by nonribosomal peptide synthetase (NRPS) pathways. For a number of such compounds, halogenated congeners have been reported along with nonhalogenated ones. In the present study, chlorinated cyanopeptolin- and/or aeruginosin-type peptides were detected by mass spectrometry in 17 out of 28 axenic strains of Microcystis. In these strains, a halogenase gene was identified between 2 genes coding for NRPS modules in respective gene clusters, whereas it was consistently absent when the strains produced only nonchlorinated corresponding congeners. Nucleotide sequences were obtained for 12 complete halogenase genes and 14 intermodule regions of gene clusters lacking a halogenase gene or containing only fragments of it. When a halogenase gene was found absent, a specific, identical excision pattern was observed for both synthetase gene clusters in most strains. A phylogenetic analysis including other bacterial halogenases showed that the NRPS-related halogenases of Microcystis form a monophyletic group divided into 2 subgroups, corresponding to either the cyanopeptolin or the aeruginosin peptide synthetases. The distribution of these peptide synthetase gene clusters, among the tested Microcystis strains, was found in relative agreement with their phylogeny reconstructed from 16S–23S rDNA intergenic spacer sequences, whereas the distribution of the associated halogenase genes appears to be sporadic. The presented data suggest that in cyanobacteria these prevalent halogenase genes originated from an ancient horizontal gene transfer followed by duplication in the cyanobacterial lineage. We propose an evolutionary scenario implying repeated gene losses to explain the distribution of halogenase genes in 2 NRPS gene clusters that subsequently defines the seemingly erratic production of halogenated and nonhalogenated aeruginosins and cyanopeptolins among Microcystis strains.

Key Words: halogenase • cyanopeptolin • aeruginosin • DNA rearrangement • secondary peptide metabolite • chlorination • internal transcribed spacer • phylogeny


1 Present address: Anagnostec GmbH, Am Mühlenberg 11, Potsdam, Germany.

Claudia Schmidt-Dannert, Associate Editor


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Appl. Environ. Microbiol.Home page
K. Ishida, M. Welker, G. Christiansen, S. Cadel-Six, C. Bouchier, E. Dittmann, C. Hertweck, and N. Tandeau de Marsac
Plasticity and Evolution of Aeruginosin Biosynthesis in Cyanobacteria
Appl. Envir. Microbiol., April 1, 2009; 75(7): 2017 - 2026.
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