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Applied and Environmental Microbiology, February 2008, p. 716-722, Vol. 74, No. 3
0099-2240/08/$08.00+0     doi:10.1128/AEM.01988-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Characterization of the Gene Cluster Responsible for Cylindrospermopsin Biosynthesis{triangledown}

Troco Kaan Mihali, Ralf Kellmann,{dagger} Julia Muenchhoff, Kevin D. Barrow, and Brett A. Neilan*

The University of New South Wales, School of Biotechnology and Biomolecular Sciences, Sydney, New South Wales 2052, Australia

Received 30 August 2007/ Accepted 21 November 2007

Toxic cyanobacterial blooms cause economic losses and pose significant public health threats on a global scale. Characterization of the gene cluster for the biosynthesis of the cyanobacterial toxin cylindrospermopsin (cyr) in Cylindrospermopsis raciborskii AWT205 is described, and the complete biosynthetic pathway is proposed. The cyr gene cluster spans 43 kb and is comprised of 15 open reading frames containing genes required for the biosynthesis, regulation, and export of the toxin. Biosynthesis is initiated via an amidinotransfer onto glycine followed by five polyketide extensions and subsequent reductions, and rings are formed via Michael additions in a stepwise manner. The uracil ring is formed by a novel pyrimidine biosynthesis mechanism and tailoring reactions, including sulfation and hydroxylation that complete biosynthesis. These findings enable the design of toxic strain-specific probes and allow the future study of the regulation and biological role of cylindrospermopsin.


* Corresponding author. Mailing address: The University of New South Wales, School of Biotechnology and Biomolecular Sciences, Sydney, New South Wales 2052, Australia. Phone: 61 2 9385 3235. Fax: 61 2 9385 1591. E-mail: b.neilan{at}unsw.edu.au

{triangledown} Published ahead of print on 7 December 2007.

{dagger} Present address: The University of Bergen, Department of Molecular Biology, 5020 Bergen, Norway.


Applied and Environmental Microbiology, February 2008, p. 716-722, Vol. 74, No. 3
0099-2240/08/$08.00+0     doi:10.1128/AEM.01988-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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