Cprp-An Unusual, Repetitive Protein Which Impacts Pleuromutilin Biosynthesis in the Basidiomycete .

Interrogation of an EST database for identified a putative homolog to the unusual stress response gene from yeast; , as being upregulated under pleuromutilin production conditions. Silencing of this gene, named , produced a population of transformants which demonstrated significantly reduced pleuromutilin production. Attempts to complement a mutant strain (strain Y16748) with were hampered by the lack of a clearly identifiable mutant phenotype, but interestingly, overexpression of either or in Y16748 led to a conspicuous and comparable reduction in growth rate. This observation, combined with the known role of DDR48 proteins from a range of fungal species in nutrient starvation and stress responses, raises the possibility that this family of proteins plays a role in triggering oligotrophic growth. Localization studies the production of a Cprp:GFP fusion protein in showed clear localization adjacent to the hyphal septa and, to a lesser extent, cell walls, which is consistent with the identification of DDR48 as a cell wall-associated protein in various yeast species. To our knowledge this is the first study demonstrating that a DDR48-like protein plays a role in the regulation of a secondary metabolite, and represents the first DDR48-like protein from a basidiomycete. Potential homologs can be identified across much of the Dikarya, suggesting that this unusual protein may play a central role in regulating both primary and secondary metabolism in fungi.