Characterization of the gene cluster responsible for cylindrospermopsin biosynthesis.
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.
Mihali
Troco Kaan
TK
The University of New South Wales, School of Biotechnology and Biomolecular Sciences, Sydney, New South Wales 2052, Australia.
Kellmann
Ralf
R
Muenchhoff
Julia
J
Barrow
Kevin D
KD
Neilan
Brett A
BA
D000470:Alkaloids; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000737:chemistry; D000087522:Cyanobacteria Toxins; D046891:Cylindrospermopsis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008387:Marine Toxins / Q000096:biosynthesis / Q000737:chemistry; D052998:Microcystins / Q000096:biosynthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D005810:Multigene Family; D017422:Sequence Analysis, DNA; D014498:Uracil / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry
D000470:Alkaloids; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; C089595:cylindrospermopsin; D014498:Uracil