SWD1 epigenetically chords fungal morphogenesis, aflatoxin biosynthesis, metabolism, and virulence of Aspergillus flavus

As the main producer of aflatoxins, Aspergillus flavus is also one of the most important causes of invasive and non-invasive aspergillosis. Therefore, it is crucial to unravel the regulatory mechanisms of growth, metabolism, and pathogenicity of A. flavus. SWD1 is highly conserved across species for maintaining COMPASS methyltransferase activity, but the bio-function of SWD1 in A. flavus has not been explored. Through genetic analysis, this study revealed that SWD1 is involved in fungal morphogenesis and AFB1 biosynthesis by regulating the orthodox pathways through H3K4me1-3. Stresses sensitivity and crop models analysis revealed that SWD1 is a key regulator for the resistance of A. flavus to adapt to extreme adverse environments and to colonize crop kernels. It also revealed that the WD40 domain and 25 aa highly conserved sequence are indispensable for SWD1 in the regulation of mycotoxin bio-synthesis and fungal virulence. Metabolomic analysis inferred that SWD1 is crucial for the biosynthesis of numerous primary and secondary metabolites, regulates biological functions by reshaping the whole metabolic process, and may inhibit fungal virulence by inducing the apoptosis of mycelia through the inducer sphingosine. This study elucidates the epigenetic mechanism of SWD1 in regulating fungal pathogenicity and mycotoxin biosynthesis, and provides a potential novel target for controlling the virulence of A. flavus.