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Fus3 regulates aflatoxin biosynthesis by controlling the substrate supply in Aspergillus flavus

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Recently, the research team of Prof. Fuguo Xing, the innovation team of Mycotoxin Prevention and Control in Agro-Products Research Team IFST, revealed the regulatory mechanism of Fus3 kinase on mycotoxin. The relevant results were published in the journal Microbiology Spectrum (IF2020: 7.17) with the title “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”.

The Fus3-MAP kinase module is a conserved phosphorylation signal system in eukaryotes. Aspergillus flavus could produce aflatoxins (AFs), which seriously threaten human and animal health. In this study, the Ste50-Ste11-Ste7-Fus3 protein interactions and phosphorylations were confirmed by Y2H and phosphoproteome, and the possible phosphorylation motifs and potential targets of Fus3 were identified, which indicated Fus3 responding to diverse environment stresses in Aspergillus. Importantly, we partly revealed the mechanism of Fus3 positive regulation on AFs biosynthesis. The substrate of AFs, acetyl-CoA and malonyl-CoA, were significantly decreased in fus3 null-deletion and site-mutagenesis strains, and the genes involved in acetyl-CoA and malonyl-CoA biosynthesis, were significantly down-regulated at transcriptional or phosphorylation levels. The acetyl-CoA carboxylase, AccA might be the potential phosphorylation target of Fus3 All results suggested that Fus3 could affect AFs biosynthesis relying on the regulation of AFs substrates supply, rather than the effect of AFs cluster expressions.

Ph. D candidate Longxue Ma and Associate Prof. Xu Li were the co-first authors, and Prof. Fuguo Xing was as the corresponding author. This work was supported by National Natural Science Foundation of China (31972179, 32001813), the National Key R&D Program of China (2016YFD0400105), the National Peanut Industrial Technology System (CARS-13), Agricultural Science and Technology Innovation Program (CAAS-ASTIP-2020-IFST-03), and Qingdao Science and Technology Benefit the People Demonstration and Guidance Special Project (21-1-4-NY-4-NSH).

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Fig. 1 The interaction and phosphorylation of Fus3-MAPK cascade.

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Fig.2 Transcriptome and phosphoproteome analyses of Fus3

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Fig. 3 The regulatory mechanism of Fus3 on aflatoxins biosynthesis