Fus3, as a Critical Kinase in MAPK Cascade, Regulates Aflatoxin Biosynthesis by Controlling the Substrate Supply in Aspergillus flavus, Rather than the Cluster Genes Modulation.
Fus3, as a Critical Kinase in MAPK Cascade, Regulates Aflatoxin Biosynthesis by Controlling the Substrate Supply in Aspergillus flavus, Rather than the Cluster Genes Modulation.
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Fus3作为MAPK级联反应中的关键激酶，通过调控黄曲霉的底物供应来调控黄曲霉毒素的生物合成，而不是通过调控簇基因。
DOI：
10.1128/spectrum.01269-21
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发表时间：
2022-02-23
影响因子：
3.7
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Ma L;Li X;Xing F;Ma J;Ma X;Jiang Y
Fus3-MAP激酶模块是真核生物中保守的磷酸化信号系统，可响应环境应激以及从外膜到细胞核的外部信号转导。黄曲霉能产生黄曲霉毒素(AF)，严重威胁人类和动物健康。在本研究中，我们确定了Fus3的功能，证实了Ste50-Ste11-Ste7-Fus3蛋白相互作用和磷酸化，并探讨了Fus3可能的磷酸化基序和潜在靶点。本研究部分揭示了Fus3对AF生物合成的调控机制。 Δfus3 中 AF 的产生下调，但大多数 AF 簇基因的转录表达上调。值得注意的是，在fus3缺陷菌株中，AF的底物乙酰辅酶A和丙二酰辅酶A的水平显着降低。参与乙酰辅酶A和丙二酰辅酶A生物合成的基因在转录或磷酸化水平上显着下调。具体而言，AccA 可能是 Fus3 的直接靶点，导致乙酰辅酶 A 羧化酶活性在零缺失和位点诱变菌株中降低。结果表明，Fus3可以直接或间接调节乙酰辅酶A和丙二酰辅酶A生物合成基因的表达，进而影响AF的产生，依赖于AF底物的调节而不是AF簇基因的调节。重要性 黄曲霉是一种重要的腐生真菌，可产生黄曲霉毒素 (AF)，威胁食品和饲料安全。 MAP（丝裂原激活蛋白）激酶对于真菌适应不同环境至关重要。 Fus3 作为 MAPK 级联的末端激酶，与其他 MAPK 模块相互作用并磷酸化下游靶标。我们提供的证据表明Fus3可以通过调节乙酰辅酶A和丙二酰辅酶A的产生来影响AF生物合成，但这并不依赖于AF生物合成基因的调节。我们的结果部分揭示了Fus3对AF生物合成的调节机制，并提供了一种新的AF调节模式，这可能有助于发现控制黄曲霉和AF污染的新策略。
The Fus3-MAP kinase module is a conserved phosphorylation signal system in eukaryotes that responds to environmental stress and transduction of external signals from the outer membrane to the nucleus. Aspergillus flavus can produce aflatoxins (AF), which seriously threaten human and animal health. In this study, we determined the functions of Fus3, confirmed Ste50-Ste11-Ste7-Fus3 protein interactions and phosphorylation, and explored the possible phosphorylation motifs and potential targets of Fus3. The regulatory mechanism of Fus3 on the biosynthesis of AF was partly revealed in this study. AF production was downregulated in Δfus3, but the transcriptional expression of most AF cluster genes was upregulated. It is notable that the levels of acetyl-CoA and malonyl-CoA, the substrates of AF, were significantly decreased in fus3 defective strains. Genes involved in acetyl-CoA and malonyl-CoA biosynthesis were significantly downregulated at transcriptional or phosphorylation levels. Specifically, AccA might be a direct target of Fus3, which led to acetyl-CoA carboxylase activities were decreased in null-deletion and site mutagenesis strains. The results concluded that Fus3 could regulate the expression of acetyl-CoA and malonyl-CoA biosynthetic genes directly or indirectly, and then affect the AF production that relies on the regulation of AF substrate rather than the modulation of AF cluster genes. IMPORTANCE Aspergillus flavus is an important saprophytic fungus that produces aflatoxins (AF), which threaten food and feed safety. MAP (mitogen-activated protein) kanases are essential for fungal adaptation to diverse environments. Fus3, as the terminal kinase of a MAPK cascade, interacts with other MAPK modules and phosphorylates downstream targets. We provide evidence that Fus3 could affect AF biosynthesis by regulating the production of acetyl-CoA and malonyl-CoA, but this does not depend on the regulation of AF biosynthetic genes. Our results partly reveal the regulatory mechanism of Fus3 on AF biosynthesis and provide a novel AF modulation pattern, which may contribute to the discovery of new strategies in controlling A. flavus and AF contamination.
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影响因子：
64.5
作者：
Good M;Tang G;Singleton J;Reményi A;Lim WA
通讯作者：
Lim WA
影响因子：
3.4
作者：
Frawley, Dean;Greco, Claudio;Bayram, Ozgur
通讯作者：
Bayram, Ozgur
DOI：
10.1073/pnas.0910097107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Bourrellier, Ana Belen Feria;Valot, Benoit;Hodges, Michael
通讯作者：
Hodges, Michael
影响因子：
16
作者：
Hao, Nan;Nayak, Sujata;Dohlman, Henrik G.
通讯作者：
Dohlman, Henrik G.
影响因子：
3.7
作者：
Altwasser R;Baldin C;Weber J;Guthke R;Kniemeyer O;Brakhage AA;Linde J;Valiante V
通讯作者：
Valiante V