The target of rapamycin signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity in Aspergillus flavus

Abstract

The target of the rapamycin (TOR) signaling pathway is highly conserved and important in eukaryotes. It is involved in the regulation of various biological processes. However, systematic studies on this pathway in the genus Aspergillus have not been reported. Here, we identified and characterized nine genes encoding components of the TOR pathway in A. flavus, and investigated their biological, genetic and biochemical functions. The FK506-binding protein FKBP3 and its lysine succinylation are important for aflatoxin production and rapamycin resistance. The Tor kinase plays a central role in the global regulation of growth, spore production, aflatoxin biosynthesis and rapamycin stress. As a major downstream effector molecule of Tor kinase, the Sch9 kinase might regulate the calcium and osmotic stress, AFB1 synthesis of A. flavus by its S_TKc, S_TK_X domains and ATP binding site at K340. We also showed that Sch9 kinase might mediate crosstalk between the TOR and the HOG signaling pathways. TapA and TipA, the other downstream components of Tor kinase, play important roles in regulating mycelial growth and sclerotia formation in A. flavus. The member of the TapA-phosphatase complexes Sit4 and Ppg1 are important for hyphal development, sexual reproduction, sclerotia formation, AFB1 biosynthesis, activation of the CWI and TOR signaling pathways in A. flavus. In addition, the another phosphatase complex Nem1/Spo7 play critical role in vegetative growth, conidiation, aflatoxin and LD biogenesis. This study provide new insights into constructing the regulatory network of the TOR signaling pathway and revealing the molecular mechanism of the pathogenicity in A. flavus.