Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism
Significance Fungi produce a vast number of different chemical compounds via secondary metabolism. These compounds are of great interest because of their potential applicability in medicine, pharmacy, and biotechnology. In addition, a number of such compounds are toxins that potentially represent severe threats to human and animal health. However, under standard cultivation conditions, fungal secondary metabolism remains largely inactive. Here, we show that the deletion of the regulator Xylanase promoter binding protein 1 (Xpp1) results in the production of significantly more secondary metabolites in terms of both number and concentration. Because homologs of Xpp1 exist in fungi with numerous bioactive secondary metabolites, our results can lead to the discovery of secondary metabolites. Fungi can produce a wide range of chemical compounds via secondary metabolism. These compounds are of major interest because of their (potential) application in medicine and biotechnology and as a potential source for new therapeutic agents and drug leads. However, under laboratory conditions, most secondary metabolism genes remain silent. This circumstance is an obstacle for the production of known metabolites and the discovery of new secondary metabolites. In this study, we describe the dual role of the transcription factor Xylanase promoter binding protein 1 (Xpp1) in the regulation of both primary and secondary metabolism of Trichoderma reesei . Xpp1 was previously described as a repressor of xylanases. Here, we provide data from an RNA-sequencing analysis suggesting that Xpp1 is an activator of primary metabolism. This finding is supported by our results from a Biolog assay determining the carbon source assimilation behavior of an xpp1 deletion strain. Furthermore, the role of Xpp1 as a repressor of secondary metabolism is shown by gene expression analyses of polyketide synthases and the determination of the secondary metabolites of xpp1 deletion and overexpression strains using an untargeted metabolomics approach. The deletion of Xpp1 resulted in the enhanced secretion of secondary metabolites in terms of diversity and quantity. Homologs of Xpp1 are found among a broad range of fungi, including the biocontrol agent Trichoderma atroviride , the plant pathogens Fusarium graminearum and Colletotrichum graminicola , the model organism Neurospora crassa , the human pathogen Sporothrix schenckii , and the ergot fungus Claviceps purpurea .
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