A Bcl-2 Associated Athanogene (bagA) Modulates Sexual Development and Secondary Metabolism in the Filamentous Fungus Aspergillus nidulans.
A Bcl-2 Associated Athanogene (bagA) Modulates Sexual Development and Secondary Metabolism in the Filamentous Fungus Aspergillus nidulans.
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DOI：
10.3389/fmicb.2018.01316
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发表时间：
2018
影响因子：
5.2
通讯作者：
Kabbage M
中科院分区：
文献类型：
--
作者：
Jain S;Wiemann P;Thill E;Williams B;Keller NP;Kabbage M
Bcl-2 相关的 athanogene (Bag) 家族是一个多功能蛋白质组，以称为 Bag 结构域 (BD) 的保守区域为特征。在此，我们讨论了模型遗传真菌构巢曲霉中 Bag 蛋白的发现和表征，我们将其命名为 BagA。 BagA 在 3D 结构、结构域组织、氨基酸特性和 Hsp70 结合表面方面与动物和植物 Bag 具有惊人的相似性。虽然 Hsp70 结合是 Bag 蛋白的共同特征，但我们的实验证据表明 BagA 不与构巢曲霉 Hsp70 合作，表明这种关联可能不是 Bag 蛋白的普遍特征。 bagA 的基因表达在性发育过程中被强烈诱导，表明其在发育过程中的作用。因此，bagA (ΔbagA) 的缺失会对性发育产生负面影响，而其过度表达则会导致有性子实体和孢子的组成型诱导。无性和有性发育与构巢曲霉的次生代谢有关。我们的数据表明，bagA 的缺失也会引起有性生长和营养生长阶段次级代谢物 (SM) 谱的改变。事实上，LC-MS 分析显示 ΔbagA 中 SM 显着富集，包括野生型菌株不产生的新代谢物。 ΔbagA 菌株中 SM 的富集特别令人感兴趣，这表明改变细胞稳态可以作为激活隐性代谢物和发现新型生物活性化合物的激发策略。总体而言，我们的结果表明丝状真菌中的 Bag 蛋白与动物和植物中的 Bag 蛋白具有共同的发育调节作用。我们还展示了 BagA 在调节构巢曲霉次生代谢方面的潜在独特作用。据我们所知，这项研究首次深入了解了丝状真菌中的 Bag 功能。
The Bcl-2 associated athanogene (Bag) family is a multifunctional group of proteins distinguished by a conserved region known as the Bag domain (BD). Herein, we discuss the discovery and characterization of a Bag protein in the model genetic fungus Aspergillus nidulans, we designated BagA. BagA shares striking similarities in 3D structure, domain organization, amino acid properties, and Hsp70 binding surfaces to animal and plant Bags. While Hsp70 binding is a common feature of Bag proteins, our experimental evidence shows that BagA does not cooperate with A. nidulans Hsp70s, suggesting this association may not be a universal feature of Bag proteins. Gene expression of bagA was strongly induced during sexual development suggesting a role in developmental processes. Accordingly, the deletion of bagA (ΔbagA) negatively impacted sexual development, while its overexpression resulted in constitutive induction of sexual fruiting bodies and spores. Asexual and sexual development was linked to secondary metabolism in A. nidulans. Our data show that the deletion of bagA also provoked an altered secondary metabolite (SM) profile in both sexual and vegetative growth phases. Indeed, LC-MS analysis showed a significant enrichment of SMs in ΔbagA, including novel metabolites not produced by wild type strain. Enrichment of SMs in ΔbagA strain is particularly intriguing and suggest that altering cellular homeostasis can be used as a provocative strategy to activate cryptic metabolites and uncover novel bioactive compounds. Overall, our results indicate that Bag proteins in filamentous fungi share developmental regulatory roles with their animal and plant counterparts. We also show a potentially unique role for BagA in modulating secondary metabolism in A. nidulans. To our knowledge, this study provides a first insight into Bag function in filamentous fungi.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1073/pnas.1318306111
发表时间：
2014-02-18
影响因子：
11.1
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通讯作者：
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影响因子：
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作者：
Gerke, Jennifer;Bayram, Oezguer;Braus, Gerhard H.
通讯作者：
Braus, Gerhard H.
影响因子：
14.8
作者：
Bok, Jin Woo;Chiang, Yi-Ming;Szewczyk, Edyta;Reyes-Domingez, Yazmid;Davidson, Ashley D.;Sanchez, James F.;Lo, Hsien-Chun;Watanabe, Kenji;Strauss, Joseph;Oakley, Berl R.;Wang, Clay C. C.;Keller, Nancy P.
通讯作者：
Keller, Nancy P.