The Kinetochore Protein Spc105, a Novel Interaction Partner of LaeA, Regulates Development and Secondary Metabolism in <i>Aspergillus flavus</i>.

Nuclear protein LaeA is known as the global regulator of secondary metabolism in <i>Aspergillus</i>. LaeA connects with VeA and VelB to form a heterotrimeric complex, which coordinates fungal development and secondary metabolism. Here, we describe a new interaction partner of LaeA, the kinetochore protein Spc105, from the aflatoxin-producing fungus <i>Aspergillus flavus</i>. We showed that in addition to involvement in nuclear division, Spc105 is required for normal conidiophore development and sclerotia production of <i>A. flavus</i>. Moreover, Spc105 positively regulates the production of secondary metabolites such as aflatoxin and kojic acid, and negatively regulates the production of cyclopiazonic acid. Transcriptome analysis of the <i>&#x394;spc105</i> strain revealed that 23 backbone genes were differentially expressed, corresponding to 19 of the predicted 56 secondary metabolite gene clusters, suggesting a broad regulatory role of Spc105 in secondary metabolism. Notably, the reduced expression of <i>laeA</i> in our transcriptome data led to the discovery of the correlation between Spc105 and LaeA, and double mutant analysis indicated a functional interdependence between Spc105 and LaeA. Further, <i>in vitro</i> and <i>in vivo</i> protein interaction assays revealed that Spc105 interacts directly with the <i>S</i>-adenosylmethionine (SAM)-binding domain of LaeA, and that the leucine zipper motif in Spc105 is required for this interaction. The Spc105-LaeA interaction identified in our study indicates a cooperative interplay of distinct regulators in <i>A. flavus</i>, providing new insights into fungal secondary metabolism regulation networks.