Feed or fight - light, nutrients and toxins in fungi

In their natural habitat, fungi constantly face the challenge to outcompete other organisms in complex ecosystems. Therefore they developed powerful enzyme systems for degradation of substrate, which provide for fast growth and efficient colonization of their environment. However, also their ability to produce toxic chemicals (secondary metabolites) serves as defense against competitors. Our studies with Trichoderma reesei (Hypocrea jecorina), a model organism for investigation of plant cell wall degradation and the interplay between light response and metabolism, revealed a light regulated secondary metabolite gene cluster. Transcription of the genes of this cluster is repressed by the photoreceptors BLR1 and BLR2 in light. In darkness, however, this cluster is regulated by the carbon catabolite repressor CRE1 and the cAMP pathway component protein kinase A (PKA). Consequently, a tightly regulated mechanism for balancing resources for nutrient acquisition (feed) and biosynthesis of secondary metabolites (fight) appears to be operative and its effect is dependent on light. In the course of the proposed project we intend to evaluate this hypothesis. We will investigate the light dependent posttranslational regulation and function of CRE1, as well as its assumed direct or indirect interplay with the photoreceptor BLR1. Metabolomic analyses will complement these studies and reveal the secondary metabolite profile of T. reesei as well as the structure of the secondary metabolite produced by the two polyketide synthetases as central components. In order to understand secondary metabolite production in T. reesei, the influence of light and CRE1 on this process in T. reesei in general shall be studied. Therefore we will investigate the function of CRE1 in chromatin rearrangement, which is already known from cellulase regulation, in a broader context also considering the involvement of photoreceptors. Paralleling the studies on secondary metabolism, we will also survey cellulase gene expression as a model output pathway for nutrient degradation throughout the project. This strategy will allow us to put substrate degradation and secondary metabolism in context and thereby gain intriguing new insights into the balance of investing resources in growth or fending off competitors during the life of a fungus.

The natural habitat of fungi is teeming with life beneficial and pathogenic microbes, plants, but also higher organisms are competing with them for nutrients and space. To survive and succeed in this environment, fungi developed efficient enzymes for degradation of dead biomass, they produce signaling compounds to communicate with other organisms and they secrete harmful metabolites to fend off competitors. If sufficient nutrients are available, fungi repress the production of enzymes by a mechanism called carbon catabolite repression. Enzymes produced by fungi are used for detergents, in food and feed and last but not least in the production of biofuels. The metabolites produced can save our lives as antibiotics and pharmaceuticals, but can also be very harmful in case of mycotoxins. Therefore we investigated the regulation of enzyme production in the filamentous fungus Trichoderma reesei, which is one of the most important fungal production organisms for enzymes worldwide. We studied the interrelationship of enzyme production with secondary metabolite production to learn whether feeding is connected to fighting and how resources are balanced between these tasks. In particular, we studied a genomic cluster, which is responsible for production of secondary metabolites and also regulated by the carbon catabolite repressor CRE1. We found that this cluster is involved in production of trichodimerol and dihydrotrichotetronine, but impacts secondary metabolite production also more generally by the function of the transcription factor YPR2. Our data indicate moreover, that there is a feedback mechanism that involves environmental sensing for balancing of metabolite production and signaling. In several cases we found that genes involved in regulation of enzyme production influence secondary metabolite secretion as well, indicating that fungi distribute their resources carefully between feeding and fighting. Besides individual regulators we investigated if epigenetic regulation changes on different nutrient sources and in light and darkness, which is indeed the case and will be studied further. In summary our research showed that regulation of secondary metabolism is not independent from enzyme production and subject to modulation by light in T. reesei. Our findings paved the way for further research towards efficient enzyme production without interference by harmful metabolites and also for improvement of production of antibiotics and reduction of mycotoxins.