Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism

Abstract

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 RNAsequencing 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.transcription factor | secondary metabolism | low molecular compounds | fungi | gene regulation F ungi are prominent producers of a broad variety of so-called secondary metabolites (1, 2). They are highly variable in structure and effects but share the following common feature: they are produced via the secondary metabolism (3, 4). Whereas primary metabolites are shared between all living cells, secondary metabolites are highly diverse and frequently produced by a limited number of species or cell types. Fungi use secondary metabolites for different purposes [e.g., protection against predation (5) or harsh environments (6), communication (7), competition and toxicity against bacteria (8) and other fungi (9), and pathogenicity (10)]. Some fungal secondary metabolites have toxic characteristics, such as aflatoxins, fumonisins, trichothecenes, fusarins, zearalenone, and ergot alkaloids (11-16), whereas other secondary metabolites are of major interest because of their potential application in the treatment of infectious diseases [e.g., antibiotics (17)] or cancer [e.g., immunosuppressants (18)] and as a potential source for novel therapeutic agents and drug leads (19). Interestingly, some of these natural products have already been used by ancient human populations (20). Numerous new compounds have been identified within the last decade that are now applied by the biotechnology and pharma...

Fusarium virguliforme Transcriptional Plasticity Is Revealed by Host Colonization of Maize versus Soybean

“…During host colonization, fungal plant pathogens elicit an array of symptoms in the plant, many of which stem not only from the modulation of the plant immune system but also from reprogramming of host development processes (Oliver and Ipcho, 2004;Horbach et al, 2011;Cordovez et al, 2017). Indeed, while studies surveying single trait interactions have highlighted key processes and pathways critical to pathogenesis of fungi in plants (Derntl et al, 2017;Fang et al, 2017), genomic and transcriptomic studies suggest fungi have a complex and elaborate infection program (Brown et al, 2017;Chowdhury et al, 2017). Comparative transcriptomics during fungal colonization have revealed that infection programs vary by fungal lifestyle, suggesting that induced pathways diverge within biotrophic, hemibiotrophic, and/or necrotrophic interactions.…”

Novel approach in whole genome mining and transcriptome analysis reveal conserved RiPPs in Trichoderma spp

“…The RNASeq data used in this study was generated in a previous study by Derntl et al [23]. Therein the wildtype like T. reesei strain QM6a Δtmus53 strain [34] cultivated in Mandels-Andreotti medium [35] containing 1% carboxy methyl cellulose as carbon source.…”

“…After 48 h of solid-state incubation at 30°C, the RNA was isolated using the RNeasy Plant Mini Kit (Quiagen) and libraries were prepared using a TruSeq Stranded mRNA Sample Prep Kit including poly (A) enrichment (Illumina). The libraries were sequenced on a NextSeq500 instrument (Illumina) with paired-end 75 nt long reads [23].…”

“…After cross-referencing the individual results, we predicted potential RiPP precursor peptides. These sequences were further refined by using previously published RNASeq data [23] and thereby providing a comprehensive highly probable in silico prediction backed up with genomic and transcriptional data.…”

In silico prediction and characterisation of secondary metabolite clusters in the plant pathogenic fungus Verticillium dahliae

“…In contrast to primary metabolites, SMs are often considered as non-essential for fungal growth, development or reproduction. However, SMs can be crucial for long-term survival in competitive fungal niches (Fox and Howlett, 2008; Ponts, 2015; Derntl et al, 2017). SMs produced by plant pathogenic fungi are of particular interest as they may contribute to virulence, leading to crop losses and threatening food security (Ponts, 2015; Pusztahelyi et al, 2015).…”