Role of urdA in regulation of development and secondary metabolism in Aspergillus nidulans

Advisors: Ana M. Calvo.Committee members: Oier Etxebeste; Yanbin Yin.Includes illustrations.Includes bibliographical references.The genus Aspergillus includes important agricultural plant pathogens, such as Aspergillus flavus, and also opportunistic human pathogens, for instance A. fumigatus. These organisms synthesize a wide range of secondary metabolites, including harmful mycotoxins. The production of these secondary metabolites as well as developmental processes are subject to a complex genetic regulation responsive to different intracellular and extracellular signals. The goal of my study is the characterization of the urdA gene, which encodes a putative Helix-loop-helix DNA binding domain protein, in the filamentous model fungus Aspergillus nidulans. Bioinformatics analyses suggests that urdA is discrete to the genus Aspergillus and few other fungal genera. The results of this study revealed that urdA is involved in the regulation of morphological development in strain with a wild-type genetic background (veA+). The urdA deletion mutant (DeltaurdA) presented a reduction in conidiation with respect to the control. Overexpression of brlA reestablished conidiation in the absence of urdA. Production of cleisthothecia was drastically increased in DeltaurdA, even in the presence of light, condition that reduces sexual development in this organism. Light also represses the production of the mycotoxin sterigmatocystin (ST) in A. nidulans wild-type under the experimental conditions assayed. However, DeltaurdA produced similar ST levels in the light as those observed when the cultures were incubated in the dark, indicating that urdA influences the biosynthesis of ST, mediating the response to external stimuli such as light. In addition, although, urdA does not affect penicillin production, this gene regulates the production of several unknown secondary metabolites. Interestingly, urdA affects the cell abundance and distribution of VeA, a global regulatory protein conserved in many fungi that controls development and secondary metabolism. Furthermore, our genetics studies indicate that veA appears epistatic to urdA, although both regulator also conduct independent roles in A. nidulans..M.S. (Master of Science