Abstract In filamentous fungi, asexual development involves morphological differentiation and metabolic changes leading to the formation of asexual spores. The process of asexual spore formation in Aspergillus is precisely regulated by multiple transcription factors (TFs), including VosA, VelB, and WetA, and these three TFs are key regulators of the formation and maturation of asexual spores (conidia) in Aspergillus including the model fungus Aspergillus nidulans . To gain a mechanistic insight on the complex regulatory roles of these TFs in asexual spores, we conducted genome-wide studies on the expression, protein-DNA interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation-sequencing data have revealed that the three TFs directly or indirectly regulate the expression of genes associated with spore-wall formation/integrity, asexual development, and secondary metabolism. In addition, metabolomics analyses of wild-type and mutant conidia indicate that these three TFs regulate a diverse array of primary and secondary metabolism. In summary, WetA, VosA, and VelB play inter-dependent and distinct roles governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia. Importance Filamentous fungi produce a vast number of asexual spores that act as reproductive and propagator cells. These spores affect humans, due to the infectious or allergenic nature of the propagule. Aspergillus species produce asexual spores called conidia and their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by spore-specific transcription factors. To understand the underlying global regulatory programs and cellular outcomes associated with conidia formation, functional genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans . Our results show that the fungus specific WetA/VosA/VelB transcription factors govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the genetic regulatory networks about how morphological developments and metabolic changes are coordinated in fungi. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin-producer Aspergillus flavus .

Transcriptomic, protein-DNA interaction, and metabolomic studies of VosA, VelB, and WetA in Aspergillus nidulans asexual spores