调控黄曲霉毒素合成及氧化应激双功能转录因子的鉴定与功能研究

项目名称： 调控黄曲霉毒素合成及氧化应激双功能转录因子的鉴定与功能研究

项目编号： No.31470198

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 贺竹梅

作者单位： 中山大学

项目金额： 85万元

中文摘要： 黄曲霉毒素生物合成调控机制的研究已成为微生物次级代谢调控研究的模型。研究表明，真菌次级代谢与氧化压力的细胞响应之间存在密切关联，应对氧化压力的转录因子也参与了对次级代谢的调控。我们的前期研究表明，抗氧化剂没食子酸处理黄曲霉后，黄曲霉毒素的合成受到抑制及引起氧化应激相关酶活性的改变，并且造成20个未知功能转录因子基因的转录发生了显著差异表达。本项目从这20个转录因子基因出发，以黄曲霉毒素生物合成调控网络为中心，通过系列分子生物学和分子遗传学技术如基因敲除、转录组测序、靶基因筛选等，鉴定出在黄曲霉毒素生物合成及应对氧化压力中起双重调控功能的转录因子，重点研究2-3个关键双功能转录因子及其靶标基因在黄曲霉毒素合成代谢及应对氧化压力中的功能，并在此基础上阐明黄曲霉在应对氧化压力时AF合成的胞内信号转导途径。本项目将为最终揭示黄曲霉毒素生物合成调控机制及其与氧化应激的共调控机制提供理论基础。

中文关键词： 黄曲霉毒素；生物合成；氧化应激；转录因子；基因表达调控

英文摘要： The regulation of aflatoxin biosynthesis has become a model in elucidating the regulation of secondary metabolite biosynthesis in micro-organisms. It had been showed that there was a strong relationship between the biosynthesis of secondary metabolism and the intracellular oxidative stress in fungi, and the transcription factors that response to oxidative stress played an important role in regulating the secondary metabolite biosynthesis. The secondary metabolism was also considered as the secondary line of the defense to oxidative stress. Our previous studies showed that the aflatoxin biosynthesis was dramatically inhibited and the activities of the oxidative stress related enzymes were greatly changed after Aspergillus flavus was treated with the antioxidant gallic acid. We also found that 20 genes, encoding transcription factor with unknown function were significantly differently transcribed after treatment with gallic acid, which indicated that these transcription factors may play an important role in regulating aflatoxin biosynthesis. This project will depart from these 20 genes for identifying transcription factors with double-function in regulating the aflatoxin biosynthesis and response to oxidative stress. We will focus on exploring the functions of 2 to 3 novel double-functional transcription factors and their target genes by using the technology of molecular biology and genetics. Finally, we will construct the regulatory network coordinating the expression of genes involved in aflatoxin biosynthesis and the oxidative stress in A. flavus. This study will provide a theoretical basis for elucidating the regulatory mechanism of the aflatoxin biosynthesis and its relationship with oxidative stress.

英文关键词： aflatoxin;biosynthesis;oxidative stress;transcription factor;gene expression regulation