Mihali Troco Kaan, Kellmann Ralf, Muenchhoff Julia, Barrow Kevin D, Neilan Brett A
The University of New South Wales, School of Biotechnology and Biomolecular Sciences, Sydney, New South Wales 2052, Australia.
Appl Environ Microbiol. 2008 Feb;74(3):716-22. doi: 10.1128/AEM.01988-07. Epub 2007 Dec 7.
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.
有毒蓝藻水华在全球范围内造成经济损失并构成重大公共卫生威胁。本文描述了莱氏柱孢藻AWT205中蓝藻毒素柱孢藻毒素（cyr）生物合成基因簇的特征，并提出了完整的生物合成途径。cyr基因簇跨度为43 kb，由15个开放阅读框组成，包含毒素生物合成、调控和输出所需的基因。生物合成通过将脒基转移到甘氨酸上开始，随后进行五次聚酮链延伸和后续还原反应，并通过迈克尔加成逐步形成环。尿嘧啶环通过一种新型嘧啶生物合成机制和修饰反应形成，包括完成生物合成的硫酸化和羟基化反应。这些发现有助于设计针对有毒菌株的探针，并为未来研究柱孢藻毒素的调控和生物学作用提供可能。
