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Dimeric basic leucine zipper (bZIP) proteins are conserved transcriptional enhancers found in all eukaryotes. A recently reported and novel function for bZIPs is association of these proteins with secondary metabolite production in filamentous fungi. In particular a Yap-like bZIP termed RsmA ( r estorer of  s econdary  m etabolism A) was identified in  Aspergillus nidulans  that positively regulates the carcinogen sterigmatocystin. To assess for conserved function for RsmA, we examined a role of this protein in secondary metabolism in the pathogen  A. fumigatus.  RsmA was found to positively regulate gliotoxin where overexpression (OE) of  rsmA  led to 2–100 fold increases of twelve  gli  cluster metabolites in culture medium including the newly identified  gli  metabolite cyclo(L-Phe-L-Ser). Lungs from both wild type and  OErsmA  infected mice contained gliotoxin (2.3 fold higher in  OErsmA  treatment) as well as the gliotoxin precursor cyclo(L-Phe-L-Ser) (3.2 fold higher in  OErsmA  treatment). The data here presents a conserved role for RsmA in secondary metabolite cluster activation and suggests cyclo(L-Phe-L-Ser) may serve as an alternative marker for diagnosis of invasive aspergillosis.

plos one

RsmA Regulates Aspergillus fumigatus Gliotoxin Cluster Metabolites Including Cyclo(L-Phe-L-Ser), a Potential New Diagnostic Marker for Invasive Aspergillosis