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A key role for vesicles in fungal secondary metabolism

机译:囊泡在真菌次级代谢中的关键作用

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摘要

Eukaryotes have evolved highly conserved vesicle transport machinery to deliver proteins to the vacuole. In this study we show that the filamentous fungus Aspergillus parasiticus employs this delivery system to perform new cellular functions, the synthesis, compartmentalization, and export of aflatoxin; this secondary metabolite is one of the most potent naturally occurring carcinogens known. Here we show that a highly pure vesicle-vacuole fraction isolated from A. parasiticus under aflatoxin-inducing conditions converts sterigmatocystin, a late intermediate in aflatoxin synthesis, to aflatoxin B_1; these organelles also compartmentalize aflatoxin. The role of vesicles in aflatoxin biosynthesis and export was confirmed by blocking vesicle-vacuole fusion using 2 independent approaches. Disruption of A. parasiticus vb1 (encodes a protein homolog of AvaA, a small GTPase known to regulate vesicle fusion in A. nidulans) or treatment with Sortin3 (blocks Vps16 function, one protein in the class C tethering complex) increased aflatoxin synthesis and export but did not affect aflatoxin gene expression, demonstrating that vesicles and not vacu-oles are primarily involved in toxin synthesis and export. We also observed that development of aflatoxigenic vesicles (aflatoxi-somes) is strongly enhanced under aflatoxin-inducing growth conditions. Coordination of aflatoxisome development with aflatoxin gene expression is at least in part mediated by Velvet (VeA), a global regulator of Aspergillus secondary metabolism. We propose a unique 2-branch model to illustrate the proposed role for VeA in regulation of aflatoxisome development and aflatoxin gene expression.
机译:真核生物已经进化出高度保守的囊泡转运机制,可以将蛋白质转运至液泡。在这项研究中,我们表明丝状真菌寄生曲霉利用这种递送系统来执行新的细胞功能,黄曲霉毒素的合成,区室化和输出。这种次级代谢产物是已知的最有效的天然致癌物之一。在这里,我们显示出在诱导黄曲霉毒素的条件下从寄生曲霉分离的高纯度囊泡-真空部分将黄曲霉毒素(一种后期的黄曲霉毒素合成中间体)转化为黄曲霉毒素B_1。这些细胞器也将黄曲霉毒素区分开。囊泡在黄曲霉毒素生物合成和输出中的作用通过使用2种独立方法阻断囊泡-真空融合来证实。破坏副寄生曲霉vb1(编码AvaA的蛋白同源物,一种已知的GTP酶,可调节构巢曲霉的囊泡融合)或用Sortin3处理(阻断Vps16功能,C类束缚复合物中的一种蛋白)可提高黄曲霉毒素的合成和输出但并未影响黄曲霉毒素基因的表达,表明囊泡而非真空核素主要参与毒素的合成和输出。我们还观察到,在诱导黄曲霉毒素的生长条件下,黄曲霉毒素囊泡(黄曲霉-体)的发育被大大增强。黄曲霉体发育与黄曲霉毒素基因表达的协调至少部分由天鹅绒菌(VeA)介导,天鹅绒菌是曲霉次生代谢的全球调节剂。我们提出了一个独特的2分支模型来说明VeA在黄曲霉小体发育和黄曲霉毒素基因表达调控中的拟议作用。

著录项

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  • 作者单位

    Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824;

    Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824;

    Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 International Environmental Research Center, Gwangju Institute of Science and Technology, Gwangju, South Korea;

    Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824;

    Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;

    Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;

    Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115;

    Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824 Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    aflatoxin biosynthesis; aflatoxisomes; compartmentalization; VeA; vb1;

    机译:黄曲霉毒素的生物合成;黄曲霉菌;分隔VeA;vb1;

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