Role of microcystin in oxidative stress acclimation in the cyanobacterium Microcystis aeruginosa

微囊藻毒素是一种由不同属的淡水蓝藻产生的多肽毒素。环七肽的生物合成是在非核糖体肽合成酶(NRPS)和聚酮合成酶(PKS)的复合体上完成的。这些毒素能够与真核蛋白磷酸酶形成共价键。我们可以证明，在产生微囊藻的蓝藻中，微囊藻毒素与一组蛋白质的半胱氨酸结合。有趣的是，结合伙伴包括卡尔文循环的关键酶Rubisco。在触发氧化应激的条件下，微囊藻毒素的结合被强烈地增强。此外，突变体中缺乏微囊藻毒素，导致对氧化应激的敏感性明显增加。综上所述，这些数据支持微囊藻毒素在天然生产者中的生理功能。我们建议微囊藻毒素具有氧化还原依赖的蛋白质调节作用。对于复杂的次生代谢物来说，这将是一个全新的功能，可以为其他次生代谢物的功能提供线索。此外，所提出的微囊藻毒素的作用可能反映了蓝藻氧化应激适应机制的生态多样性。了解微囊藻毒素的作用有助于开发新的有毒蓝藻管理策略。

Microcystin is a peptide toxin that is produced by various genera of bloom-forming freshwater cyanobacteria. The biosynthesis of the cyclic heptapeptide is achieved on a complex of non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS). The toxins are capable of forming a covalent bond to eukaryotic protein phosphatases. We could show that microcystin binds to cysteines of a set of proteins in the producing cyanobacterium Microcystis. Interestingly, the binding partners include the key enzyme of the Calvin cycle, Rubisco. Binding of microcystin is strongly enhanced under conditions triggering oxidative stress. Moreover, the lack of microcystin in the mutant leads to a clear increase in the sensitivity against oxidative stress. Together, these data support a physiological function of microcystin in the natural producer. We suggest a redox-dependent protein-modulating role for microcystin. This would be an entirely new function for a complex secondary metabolite that could provide hints on the functionality of other secondary metabolites. Moreover, the proposed role of microcystin may reflect the ecological diversity of oxidative stress acclimation mechanisms in cyanobacteria. Understanding the role of microcystin can assist in the development of new management strategies of toxic cyanobacteria.