Kellmann Ralf, Mills Toby, Neilan Brett A
School of Biotechnology and Biomolecular Sciences, Section Microbiology, The University of New South Wales, Biotechnology, Sydney, Australia.
J Mol Evol. 2006 Mar;62(3):267-80. doi: 10.1007/s00239-005-0030-6. Epub 2006 Feb 25.
The alkaloid cylindrospermopsin is the most recently discovered cyanotoxin and has caused epidemic outbreaks of human poisoning. Cylindrospermopsin producing cyanobacteria have in recent times appeared in countries all over the world where they had not been observed previously and, thus, represent a global public health concern. Three putative cylindrospermopsin biosynthesis genes, encoding an amidinotransferase (aoaA), a nonribosomal peptide synthetase (aoaB), and a polyketide synthase (aoaC), have been described. Most cyanotoxins are the product of nonribosomal peptide and polyketide synthesis, but the involvement of an amidinotransferase is novel. In the present study, functional modeling was carried out to gain insight into the mechanism of precursor recruitment in cylindrospermopsin biosynthesis. In addition, the molecular phylogenies of putative cylindrospermopsin biosynthesis genes and producer organisms were determined. The model indicated that AoaA may catalyze the formation of guanidino acetate from glycine and arginine. The catalytic site of the AoaB adenylation domain provided two aspartate residues, instead of the usual one, which may be involved in the binding of the guanidino moiety of guanidino acetate. Molecular phylogenetic analysis grouped cylindrospermopsin producing cyanobacteria into two divergent groups. Although the phylogeny of the cylindrospermopsin biosynthesis genes followed that of the producer organisms, they were less divergent, which may indicate the recent horizontal transfer of these genes.
生物碱柱孢藻毒素是最近发现的一种蓝藻毒素，已引发多起人类中毒的流行疫情。产柱孢藻毒素的蓝藻细菌近来在世界各地以前未发现过它们的国家出现，因此，这成为一个全球公共卫生问题。已描述了三个假定的柱孢藻毒素生物合成基因，分别编码一种脒基转移酶（aoaA）、一种非核糖体肽合成酶（aoaB）和一种聚酮化合物合成酶（aoaC）。大多数蓝藻毒素是非核糖体肽和聚酮化合物合成的产物，但脒基转移酶的参与是新颖的。在本研究中，进行了功能建模以深入了解柱孢藻毒素生物合成中前体募集的机制。此外，还确定了假定的柱孢藻毒素生物合成基因和产毒生物的分子系统发育。该模型表明，AoaA可能催化由甘氨酸和精氨酸形成胍基乙酸。AoaB腺苷化结构域的催化位点提供了两个天冬氨酸残基，而不是通常的一个，这可能参与胍基乙酸胍基部分的结合。分子系统发育分析将产柱孢藻毒素的蓝藻细菌分为两个不同的组。虽然柱孢藻毒素生物合成基因的系统发育与产毒生物的系统发育一致，但它们的差异较小，这可能表明这些基因最近发生了水平转移。
