Previous Article | Next Article 
Journal of Bacteriology, January 2003, p. 564-572, Vol. 185, No. 2
0021-9193/03/$08.00+0 DOI: 10.1128/JB.185.2.564-572.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Microcystin Biosynthesis in Planktothrix: Genes, Evolution, and Manipulation
Guntram Christiansen,1 Jutta Fastner,2 Marcel Erhard,3 Thomas Börner,1* and Elke Dittmann1,
Institut für Biologie (Genetik), Humboldt-Universität Berlin, D-10115 Berlin,1
Max-Volmer-Institut, Technische Universität Berlin, D-10587 Berlin,2
AnagnosTec GmbH, Im Biotechnologiepark, D-14943 Luckenwalde, Germany3
Received 1 July 2002/
Accepted 16 October 2002
Microcystins represent an extraordinarily large family of cyclic heptapeptide toxins that are nonribosomally synthesized by various cyanobacteria. Microcystins specifically inhibit the eukaryotic protein phosphatases 1 and 2A. Their outstanding variability makes them particularly useful for studies on the evolution of structure-function relationships in peptide synthetases and their genes. Analyses of microcystin synthetase genes provide valuable clues for the potential and limits of combinatorial biosynthesis. We have sequenced and analyzed 55.6 kb of the potential microcystin synthetase gene (mcy) cluster from the filamentous cyanobacterium Planktothrix agardhii CYA 126. The cluster contains genes for peptide synthetases (mcyABC), polyketide synthases (PKSs; mcyD), chimeric enzymes composed of peptide synthetase and PKS modules (mcyEG), a putative thioesterase (mcyT), a putative ABC transporter (mcyH), and a putative peptide-modifying enzyme (mcyJ). The gene content and arrangement and the sequence of specific domains in the gene products differ from those of the mcy cluster in Microcystis, a unicellular cyanobacterium. The data suggest an evolution of mcy clusters from, rather than to, genes for nodularin (a related pentapeptide) biosynthesis. Our data do not support the idea of horizontal gene transfer of complete mcy gene clusters between the genera. We have established a protocol for stable genetic transformation of Planktothrix, a genus that is characterized by multicellular filaments exhibiting continuous motility. Targeted mutation of mcyJ revealed its function as a gene coding for a O-methyltransferase. The mutant cells produce a novel microcystin variant exhibiting reduced inhibitory activity toward protein phosphatases.
* Corresponding author. Mailing address: Institut für Biologie (Genetik), Humboldt-Universität Berlin, Chausseestr. 117, D-10115 Berlin, Germany. Phone: 49-30-2093-8140. Fax: 49-30-2093-8141. E-mail:
thomas.boerner{at}rz.hu-berlin.de.
Present address: Institut für Gewässerbiologie und Binnenfischerei, 12587 Berlin, Germany.
Journal of Bacteriology, January 2003, p. 564-572, Vol. 185, No. 2
0021-9193/03/$08.00+0 DOI: 10.1128/JB.185.2.564-572.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Sorrels, C. M., Proteau, P. J., Gerwick, W. H.
(2009). Organization, Evolution, and Expression Analysis of the Biosynthetic Gene Cluster for Scytonemin, a Cyanobacterial UV-Absorbing Pigment. Appl. Environ. Microbiol.
75: 4861-4869
[Abstract]
[Full Text]
-
Allender, C. J., LeCleir, G. R., Rinta-Kanto, J. M., Small, R. L., Satchwell, M. F., Boyer, G. L., Wilhelm, S. W.
(2009). Identifying the Source of Unknown Microcystin Genes and Predicting Microcystin Variants by Comparing Genes within Uncultured Cyanobacterial Cells. Appl. Environ. Microbiol.
75: 3598-3604
[Abstract]
[Full Text]
-
Christiansen, G., Molitor, C., Philmus, B., Kurmayer, R.
(2008). Nontoxic Strains of Cyanobacteria Are the Result of Major Gene Deletion Events Induced by a Transposable Element. Mol Biol Evol
25: 1695-1704
[Abstract]
[Full Text]
-
Tooming-Klunderud, A., Mikalsen, B., Kristensen, T., Jakobsen, K. S.
(2008). The mosaic structure of the mcyABC operon in Microcystis. Microbiology
154: 1886-1899
[Abstract]
[Full Text]
-
Briand, E., Gugger, M., Francois, J.-C., Bernard, C., Humbert, J.-F., Quiblier, C.
(2008). Temporal Variations in the Dynamics of Potentially Microcystin-Producing Strains in a Bloom-Forming Planktothrix agardhii (Cyanobacterium) Population. Appl. Environ. Microbiol.
74: 3839-3848
[Abstract]
[Full Text]
-
Fewer, D. P., Tooming-Klunderud, A., Jokela, J., Wahlsten, M., Rouhiainen, L., Kristensen, T., Rohrlack, T., Jakobsen, K. S., Sivonen, K.
(2008). Natural occurrence of microcystin synthetase deletion mutants capable of producing microcystins in strains of the genus Anabaena (Cyanobacteria). Microbiology
154: 1007-1014
[Abstract]
[Full Text]
-
Kaneko, T., Nakajima, N., Okamoto, S., Suzuki, I., Tanabe, Y., Tamaoki, M., Nakamura, Y., Kasai, F., Watanabe, A., Kawashima, K., Kishida, Y., Ono, A., Shimizu, Y., Takahashi, C., Minami, C., Fujishiro, T., Kohara, M., Katoh, M., Nakazaki, N., Nakayama, S., Yamada, M., Tabata, S., Watanabe, M. M.
(2008). Complete Genomic Structure of the Bloom-forming Toxic Cyanobacterium Microcystis aeruginosa NIES-843. DNA Res
0: dsm026v1-10
[Abstract]
[Full Text]
-
Rounge, T. B., Rohrlack, T., Tooming-Klunderud, A., Kristensen, T., Jakobsen, K. S.
(2007). Comparison of Cyanopeptolin Genes in Planktothrix, Microcystis, and Anabaena Strains: Evidence for Independent Evolution within Each Genus. Appl. Environ. Microbiol.
73: 7322-7330
[Abstract]
[Full Text]
-
Hotto, A. M., Satchwell, M. F., Boyer, G. L.
(2007). Molecular Characterization of Potential Microcystin-Producing Cyanobacteria in Lake Ontario Embayments and Nearshore Waters. Appl. Environ. Microbiol.
73: 4570-4578
[Abstract]
[Full Text]
-
Tang, G.-L., Cheng, Y.-Q., Shen, B.
(2007). Chain Initiation in the Leinamycin-producing Hybrid Nonribosomal Peptide/Polyketide Synthetase from Streptomyces atroolivaceus S-140: DISCRETE, MONOFUNCTIONAL ADENYLATION ENZYME AND PEPTIDYL CARRIER PROTEIN THAT DIRECTLY LOAD D-ALANINE. J. Biol. Chem.
282: 20273-20282
[Abstract]
[Full Text]
-
Tooming-Klunderud, A., Rohrlack, T., Shalchian-Tabrizi, K., Kristensen, T., Jakobsen, K. S.
(2007). Structural analysis of a non-ribosomal halogenated cyclic peptide and its putative operon from Microcystis: implications for evolution of cyanopeptolins. Microbiology
153: 1382-1393
[Abstract]
[Full Text]
-
Copp, J. N., Roberts, A. A., Marahiel, M. A., Neilan, B. A.
(2007). Characterization of PPTNs, a Cyanobacterial Phosphopantetheinyl Transferase from Nodularia spumigena NSOR10. J. Bacteriol.
189: 3133-3139
[Abstract]
[Full Text]
-
Nakasugi, K., Alexova, R., Svenson, C. J., Neilan, B. A.
(2007). Functional Analysis of PilT from the Toxic Cyanobacterium Microcystis aeruginosa PCC 7806. J. Bacteriol.
189: 1689-1697
[Abstract]
[Full Text]
-
Pearson, L. A., Barrow, K. D., Neilan, B. A.
(2007). Characterization of the 2-Hydroxy-acid Dehydrogenase McyI, Encoded within the Microcystin Biosynthesis Gene Cluster of Microcystis aeruginosa PCC7806. J. Biol. Chem.
282: 4681-4692
[Abstract]
[Full Text]
-
Rantala, A., Rajaniemi-Wacklin, P., Lyra, C., Lepisto, L., Rintala, J., Mankiewicz-Boczek, J., Sivonen, K.
(2006). Detection of Microcystin-Producing Cyanobacteria in Finnish Lakes with Genus-Specific Microcystin Synthetase Gene E (mcyE) PCR and Associations with Environmental Factors. Appl. Environ. Microbiol.
72: 6101-6110
[Abstract]
[Full Text]
-
Christiansen, G., Kurmayer, R., Liu, Q., Borner, T.
(2006). Transposons Inactivate Biosynthesis of the Nonribosomal Peptide Microcystin in Naturally Occurring Planktothrix spp.. Appl. Environ. Microbiol.
72: 117-123
[Abstract]
[Full Text]
-
Gkelis, S., Moustaka-Gouni, M., Sivonen, K., Lanaras, T.
(2005). First report of the cyanobacterium Aphanizomenon ovalisporum Forti in two Greek lakes and cyanotoxin occurrence. J PLANKTON RES
27: 1295-1300
[Abstract]
[Full Text]
-
Nakasugi, K., Neilan, B. A.
(2005). Identification of Pilus-Like Structures and Genes in Microcystis aeruginosa PCC7806. Appl. Environ. Microbiol.
71: 7621-7625
[Abstract]
[Full Text]
-
Tonk, L., Visser, P. M., Christiansen, G., Dittmann, E., Snelder, E. O. F. M., Wiedner, C., Mur, L. R., Huisman, J.
(2005). The Microcystin Composition of the Cyanobacterium Planktothrix agardhii Changes toward a More Toxic Variant with Increasing Light Intensity. Appl. Environ. Microbiol.
71: 5177-5181
[Abstract]
[Full Text]
-
Kurmayer, R., Christiansen, G., Gumpenberger, M., Fastner, J.
(2005). Genetic identification of microcystin ecotypes in toxic cyanobacteria of the genus Planktothrix. Microbiology
151: 1525-1533
[Abstract]
[Full Text]
-
Moffitt, M. C., Neilan, B. A.
(2004). Characterization of the Nodularin Synthetase Gene Cluster and Proposed Theory of the Evolution of Cyanobacterial Hepatotoxins. Appl. Environ. Microbiol.
70: 6353-6362
[Abstract]
[Full Text]
-
Oksanen, I., Jokela, J., Fewer, D. P., Wahlsten, M., Rikkinen, J., Sivonen, K.
(2004). Discovery of Rare and Highly Toxic Microcystins from Lichen-Associated Cyanobacterium Nostoc sp. Strain IO-102-I. Appl. Environ. Microbiol.
70: 5756-5763
[Abstract]
[Full Text]
-
Rouhiainen, L., Vakkilainen, T., Siemer, B. L., Buikema, W., Haselkorn, R., Sivonen, K.
(2004). Genes Coding for Hepatotoxic Heptapeptides (Microcystins) in the Cyanobacterium Anabaena Strain 90. Appl. Environ. Microbiol.
70: 686-692
[Abstract]
[Full Text]
-
Rantala, A., Fewer, D. P., Hisbergues, M., Rouhiainen, L., Vaitomaa, J., Borner, T., Sivonen, K.
(2004). Phylogenetic evidence for the early evolution of microcystin synthesis. Proc. Natl. Acad. Sci. USA
101: 568-573
[Abstract]
[Full Text]
-
Emmert, E. A. B., Klimowicz, A. K., Thomas, M. G., Handelsman, J.
(2004). Genetics of Zwittermicin A Production by Bacillus cereus. Appl. Environ. Microbiol.
70: 104-113
[Abstract]
[Full Text]
-
Vaitomaa, J., Rantala, A., Halinen, K., Rouhiainen, L., Tallberg, P., Mokelke, L., Sivonen, K.
(2003). Quantitative Real-Time PCR for Determination of Microcystin Synthetase E Copy Numbers for Microcystis and Anabaena in Lakes. Appl. Environ. Microbiol.
69: 7289-7297
[Abstract]
[Full Text]