The Insect Pathogenicity of Cordyceps militaris - a molecular, metabolic, ecological, and phylogenetic study

北虫草的昆虫致病性——分子、代谢、生态和系统发育研究

• 批准号: 1945077
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1945077
• 关键词: Insect; Pathogenicity; Cordyceps; militaris; molecular

Cordycepin, or 3'-deoxyadenosine, is a secondary metabolite secreted by the cosmopolitan entomopathogenic "caterpillar fungus" Cordyceps millitaris and closely related species. The metabolite is well known for its anti-inflammatory effects and thus has been used as both a traditional Chinese medicine for centuries and a focus of pharmacological research in recent years. However, studies on the ecological roles of cordycepin and other secondary metabolites in the infection of the insect larval host and the involvement of these on the sexual development which occurs following this process are in their infancy. Culture degeneration, a phenomenon observed in a broad range of ascomycete fungi, is the loss of ability to develop sexually and perform parts of secondary metabolism following subsequent subculturing in the vegetative state. This is a significant problematic issue in cordycepin production from laboratory and industrial-based cultures.Here, a Chinese strain of Cordyceps militaris, CM2 (MycoMedica) with high cordycepin production was successively sub-cultured on potato dextrose agar. Targeted analysis of cordycepin and associated metabolite pentostatin by liquid chromatography (LC)-coupled mass spectrometry (MS), combined with a gene expression analysis using RT-qPCR provided evidence of a link between phenotypes and gene expression of both sexual development and secondary metabolite biosynthesis. Cordycepin production was greatly reduced in degenerated, multiply-subcultured samples; although production was partially restored following long-term transfer of these to a new media type based on the host substrate (silk pupa powder agar). Significant decreases in the expression of a sexual development gene, as well as cordycepin and related biosynthesis genes were also detected. Untargeted LC-MS analysis was performed to compare degenerated and non-degenerated strains.

虫草素又称3‘-脱氧腺苷，是昆虫病原虫生虫草虫草及其近缘种所分泌的次生代谢物。这种代谢物以其抗炎作用而闻名，因此作为一种中药已有数百年的历史，近年来也是药理研究的重点。然而，虫草素和其他次生代谢产物在昆虫幼虫寄主感染过程中的生态作用以及它们对随后发生的性发育的参与的研究还处于初级阶段。培养物退化是在广泛的子囊菌真菌中观察到的一种现象，是指在随后的营养状态下继代培养后丧失有性发育和执行部分次生代谢的能力。这是虫草素实验室和工业化生产中的一个重要问题。在此，一株高产虫草素的中国北虫夏草菌株CM2(MycoMedica)在马铃薯葡萄糖琼脂上进行了继代培养。对虫草素及其相关代谢物的高效液相色谱(LC)-联用质谱仪(MS)进行靶向分析，结合RT-qPCR的基因表达分析，提供了性发育和次生代谢物生物合成的表型和基因表达之间存在联系的证据。在退化的、多次继代培养的样品中，虫草素的产量大大减少；尽管在将虫草素长期转移到基于宿主底物的新培养基类型(蚕蛹粉琼脂)后，虫草素的产量部分恢复。还检测到性发育基因以及虫草素和相关生物合成基因的表达显著下降。进行非靶向LC-MS分析以比较退化和非退化菌株。

项目成果

Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products.

• DOI: 10.21037/atm.2019.04.25
• 发表时间: 2019-04
• 期刊: Annals of translational medicine
• 作者: P. A. Wellham;Dong-Hyun Kim;M. Brock;C. D. de Moor

A Systematic Review of the Biological Effects of Cordycepin.

• DOI: 10.3390/molecules26195886
• 发表时间: 2021-09-28
• 期刊: Molecules (Basel, Switzerland)
• 作者: Radhi M;Ashraf S;Lawrence S;Tranholm AA;Wellham PAD;Hafeez A;Khamis AS;Thomas R;McWilliams D;de Moor CH
• 通讯作者: de Moor CH

Culture Degeneration Reduces Sex-Related Gene Expression, Alters Metabolite Production and Reduces Insect Pathogenic Response in Cordyceps militaris.

• DOI: 10.3390/microorganisms9081559
• 发表时间: 2021-07-22
• 期刊: Microorganisms
• 影响因子: 4.5
• 作者: Wellham PAD;Hafeez A;Gregori A;Brock M;Kim DH;Chandler D;de Moor CH
• 通讯作者: de Moor CH

Cordycepin, a metabolite of Cordyceps militaris, reduces immune-related gene expression in insects.

• DOI: 10.1016/j.jip.2020.107480
• 发表时间: 2020-11
• 期刊: Journal of invertebrate pathology
• 影响因子: 3.4
• 作者: Woolley VC;Teakle GR;Prince G;de Moor CH;Chandler D
• 通讯作者: Chandler D