A systems biology approach to dissect the morphogenetic network of Aspergillus niger that links growth with product formation

一种系统生物学方法,用于剖析黑曲霉形态发生网络,将生长与产物形成联系起来

基本信息

项目摘要

Filamentous fungi such as Aspergillus niger are harnessed as cell factories for the production of a diverse range of organic acids, proteins, and secondary metabolites. However, the adequate macroscopic fungal morphology for a given target product varies, cannot currently be generalized, and the advantages and disadvantages of mycelial and pellet cultivation have to be carefully adjusted for a given process. Hence, a rational genetic approach to predict and engineer the macroscopic morphology of filamentous fungi for bioprocesses is so far impossible.The overall objective of the proposal is to gain mechanistic insights into the link between citric acid production, protein secretion, growth and morphology of A. niger. Our comprehensive analysis of A. niger transcriptomic data uncovered that a sub-network related to citric acid biosynthesis (“citA network” contains 282 genes, 57 of which can be predicted to be important for polar growth, organelle functioning, vesicle transport, signalling, and cell wall and cell membrane integrity). Notably, 14 of these genes have a predicted function in the Golgi complex, thus allocating a specific function of this vesicle transport machinery and signalling hub in the natural capability of A. niger to overproduce and secrete citric acid. In view of the importance of the Golgi complex in vesicle transport for protein overproduction and protein secretion in A. niger, we propose that a systematic analysis of the predicted 57 “citA morphogenes” will reveal new fundamental insights into the link between citric acid biosynthesis and protein secretion with morphological decisions. Such a proposed link is highly speculative and has not been studied yet in filamentous fungi. We will exploit state-of-the-art tools which have been established in our labs for A. niger including systems biology tools (i.e. genomics, transcriptomics, metabolomics and bioinformatics), synthetic biology tools (i.e. inducible expression allowing growth- and metabolism-independent expression based on the Tet-on system), controlled bioreactor cultivations for physiological characterizations, and confocal fluorescence microscopy to study organelle localisation during misexpression of the citA morphogenes. Using such a holistic approach, which is embedded in four work packages, the role of the “citA morphogenes” for A. niger will be studied in detail to achieve the following four objectives:• Identification of morphology modulators from 57 “citA morphogenes” • Unravelling the importance of 57 “citA morphogenes” for citric acid and protein production• Unravelling the importance of selected “citA morphogenes” for vesicle trafficking, hyphal growth and pellet formation • Deduction of lead genes to rationally mould A. niger with respect to high productivityThe ultimate goal is to understand the mechanisms behind the citA sub-network that balance hyphal growth with citric acid production and protein secretion.
丝状真菌如尼日尔曲霉被用作细胞工厂,用于生产各种有机酸、蛋白质和次级代谢产物。然而,对于给定的目标产物,适当的宏观真菌形态变化,目前不能概括,并且对于给定的过程,必须仔细调整菌丝体和颗粒培养的优点和缺点。因此,一个合理的遗传方法来预测和工程丝状真菌的宏观形态的生物过程是迄今为止不可能的。尼日尔.对A.尼日尔的转录组学数据揭示了与柠檬酸生物合成相关的子网络(“citA网络”包含282个基因,其中57个可以预测对极性生长、细胞器功能、囊泡运输、信号传导以及细胞壁和细胞膜完整性是重要的)。值得注意的是,这些基因中有14个在高尔基复合体中具有预测的功能,从而在A.尼日尔木耳过量生产和分泌柠檬酸。鉴于高尔基复合体在囊泡运输中对A.尼日尔,我们提出,预测的57个“citA morphogenes”的系统分析将揭示柠檬酸生物合成和蛋白质分泌与形态决定之间的联系的新的基本见解。这种联系是高度推测性的,尚未在丝状真菌中进行研究。我们将利用我们的实验室中已经建立的最先进的工具来进行A。包括系统生物学工具(即基因组学、转录组学、代谢组学和生物信息学)、合成生物学工具(即基于Tet-on系统允许生长和代谢独立表达的诱导表达)、用于生理表征的受控生物反应器培养以及用于研究citA形态基因错误表达期间细胞器定位的共聚焦荧光显微镜。使用这样一个整体的方法,这是嵌入在四个工作包,“citA形态基因”的作用,为A。将对尼日尔进行详细研究,以实现以下四个目标: 鉴定来自57种“citA形态基因”的形态调节剂· 揭示57种“citA形态基因”对柠檬酸和蛋白质生产的重要性· 揭示选定的“citA形态基因”对囊泡运输、菌丝生长和颗粒形成的重要性· 推导先导基因,合理塑造A。最终目标是了解citA子网络背后的机制,该子网络平衡菌丝生长与柠檬酸生产和蛋白质分泌。

项目成果

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Professorin Dr.-Ing. Vera Meyer其他文献

Professorin Dr.-Ing. Vera Meyer的其他文献

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{{ truncateString('Professorin Dr.-Ing. Vera Meyer', 18)}}的其他基金

Establishment of an innovative co-cultivation platform for high-throughput identification of antimicrobial compounds
建立用于高通量鉴定抗菌化合物的创新共培养平台
  • 批准号:
    404295023
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
    Research Grants
A systems biology approach to dissect the function of the antifungal protein AnAFPfor Aspergillus niger
一种系统生物学方法来剖析黑曲霉抗真菌蛋白 AnAFP 的功能
  • 批准号:
    404869152
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
    Research Grants

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组蛋白乙酰化修饰ATG13激活自噬在牵张应力介导骨缝Gli1+干细胞成骨中的机制研究
  • 批准号:
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Journal of Integrative Plant Biology
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    31024801
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Computational Methods for Analyzing Toponome Data
  • 批准号:
    60601030
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    2006
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    17.0 万元
  • 项目类别:
    青年科学基金项目

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Caveolin-1 作为尤文肉瘤细胞适应驱动因素的背景依赖性作用
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