雷帕霉素(TOR)信号通路是高度保守的,在真核生物的多种生物过程中起着至关重要的作用。尽管意义重大,黄曲霉中TOR途径的潜在机制仍然难以捉摸。在这项研究中,我们通过鉴定和表征9个编码该通路不同成分的基因,全面分析了黄曲霉中的TOR信号通路.FK506结合蛋白Fkbp3及其赖氨酸琥珀酰化对于黄曲霉毒素的产生和雷帕霉素抗性是重要的。TorA激酶在调节生长中起着关键作用,孢子生产,黄曲霉毒素生物合成,以及对雷帕霉素和细胞膜应激的反应。作为TorA激酶的重要下游效应分子,Sch9激酶调节黄曲霉毒素B1(AFB1)的合成,黄曲霉的渗透和钙应激反应,这种调节是通过其S_TKc介导的,S_TK_X域,和K340处的ATP结合位点。我们还表明,Sch9激酶可能对高渗透压甘油(HOG)信号通路具有调节作用。TapA和TipA,TorA激酶的其他下游成分,黄花在调节细胞壁应激反应中起重要作用。此外,TapA-磷酸酶复合物的成员,SitA和Ppg1对黄曲霉的各种生物过程很重要,包括营养生长,菌核形成,AFB1生物合成,和致病性。我们还证明了SitA和Ppg1参与调节脂滴(LD)生物发生和细胞壁完整性(CWI)信号通路。此外,另一种磷酸酶复合物,Nem1/Po7,在菌丝发育中起关键作用,分生孢子,黄曲霉毒素生产,和LDs生物发生。总的来说,我们的研究为TOR信号通路的调控网络提供了重要的见解,并阐明了黄曲霉毒素生物合成的潜在分子机制。
The target of rapamycin (TOR) signaling pathway is highly conserved and plays a crucial role in diverse biological processes in eukaryotes. Despite its significance, the underlying mechanism of the TOR pathway in Aspergillus flavus remains elusive. In this study, we comprehensively analyzed the TOR signaling pathway in A. flavus by identifying and characterizing nine genes that encode distinct components of this pathway. The FK506-binding protein Fkbp3 and its lysine succinylation are important for
aflatoxin production and rapamycin resistance. The TorA kinase plays a pivotal role in the regulation of growth, spore production,
aflatoxin biosynthesis, and responses to rapamycin and cell membrane stress. As a significant downstream effector molecule of the TorA kinase, the Sch9 kinase regulates
aflatoxin B1 (AFB1) synthesis, osmotic and calcium stress response in A. flavus, and this regulation is mediated through its S_TKc, S_TK_X domains, and the ATP-binding site at K340. We also showed that the Sch9 kinase may have a regulatory impact on the high osmolarity glycerol (HOG) signaling pathway. TapA and TipA, the other downstream components of the TorA kinase, play a significant role in regulating cell wall stress response in A. flavus. Moreover, the members of the TapA-phosphatase complexes, SitA and Ppg1, are important for various biological processes in A. flavus, including vegetative growth, sclerotia formation, AFB1 biosynthesis, and pathogenicity. We also demonstrated that SitA and Ppg1 are involved in regulating lipid droplets (LDs) biogenesis and cell wall integrity (CWI) signaling pathways. In addition, another phosphatase complex, Nem1/Spo7, plays critical roles in hyphal development, conidiation,
aflatoxin production, and LDs biogenesis. Collectively, our study has provided important insight into the regulatory network of the TOR signaling pathway and has elucidated the underlying molecular mechanisms of
aflatoxin biosynthesis in A. flavus.