Institute of Biology, Department of Molecular Ecology, Humboldt University, Berlin, Germany.
PLoS One. 2011 Mar 18;6(3):e17615. doi: 10.1371/journal.pone.0017615.
Microcystins are cyanobacterial toxins that represent a serious threat to drinking water and recreational lakes worldwide. Here, we show that microcystin fulfils an important function within cells of its natural producer Microcystis. The microcystin deficient mutant ΔmcyB showed significant changes in the accumulation of proteins, including several enzymes of the Calvin cycle, phycobiliproteins and two NADPH-dependent reductases. We have discovered that microcystin binds to a number of these proteins in vivo and that the binding is strongly enhanced under high light and oxidative stress conditions. The nature of this binding was studied using extracts of a microcystin-deficient mutant in vitro. The data obtained provided clear evidence for a covalent interaction of the toxin with cysteine residues of proteins. A detailed investigation of one of the binding partners, the large subunit of RubisCO showed a lower susceptibility to proteases in the presence of microcystin in the wild type. Finally, the mutant defective in microcystin production exhibited a clearly increased sensitivity under high light conditions and after hydrogen peroxide treatment. Taken together, our data suggest a protein-modulating role for microcystin within the producing cell, which represents a new addition to the catalogue of functions that have been discussed for microbial secondary metabolites.
微囊藻毒素是一种蓝藻毒素，对全世界的饮用水和娱乐湖泊构成了严重威胁。在这里，我们表明微囊藻毒素在其天然产生菌微囊藻的细胞内发挥着重要功能。缺乏微囊藻毒素的突变体 ΔmcyB 在蛋白质的积累方面表现出显著变化，包括卡尔文循环的几种酶、藻胆蛋白和两种 NADPH 依赖性还原酶。我们发现微囊藻毒素在体内与许多这些蛋白质结合，并且在强光和氧化应激条件下结合强烈增强。这种结合的性质使用体外缺乏微囊藻毒素的突变体提取物进行了研究。获得的数据提供了毒素与蛋白质的半胱氨酸残基发生共价相互作用的明确证据。对其中一个结合伙伴Rubisco 的大亚基的详细研究表明，在存在微囊藻毒素的情况下，野生型的蛋白酶敏感性降低。最后，缺乏微囊藻毒素产生的突变体在强光条件下和过氧化氢处理后表现出明显增加的敏感性。总之，我们的数据表明微囊藻毒素在产生细胞内具有蛋白质调节作用，这是对已讨论过的微生物次生代谢物功能的新补充。
