麦角硫因毒素的毒性机制及毒性预防的生物合成策略

The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention.

作者信息

Ye Wei, Liu Taomei, Zhang Weiyang, Zhang Weimin

机构信息

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.

Department of Ocean Science and Hong Kong Branch of Southern Marine Science and Engineering Laboratory (Guangzhou), Hong Kong University of Science and Technology, Hong Kong, China.

出版信息

Int J Mol Sci. 2021 Dec 16;22(24):13510. doi: 10.3390/ijms222413510.

Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including and Thus, it is important to elucidate the toxic mechanism of gliotoxins. The toxic mechanism of gliotoxins and biosynthetic strategies to reduce the toxicity of gliotoxins and their producing strains are summarized in this review.

Gliotoxin是一种源自不同真菌的环多硫代二氧哌嗪，其特征是具有二硫键。Gliotoxin可通过基因簇进行生物合成，并由正向GliZ调节因子调控。Gliotoxin通过抑制巨噬细胞免疫功能、炎症、抗血管生成、通过产生ROS导致DNA损伤、通过抑制各种酶导致过氧化物损伤以及通过不同信号通路诱导细胞凋亡等方式表现出细胞毒性作用。另一方面，Gliotoxin在不同剂量下也可能有益。低剂量的Gliotoxin可用作抗氧化剂、用于HIV的诊断和治疗，以及未来作为抗肿瘤剂。Gliotoxin还被用于控制植物病原体，包括和因此，阐明Gliotoxin的毒性机制很重要。本综述总结了Gliotoxin的毒性机制以及降低Gliotoxin及其产生菌株毒性的生物合成策略。