A pleiotropic Regulator of Secondary Metabolism

Fungi are responsible for the production of many natural products as a result of a wide variety of species and use of various biosynthetic pathways. Numerous of these products have been identied during the last decades and are nowadays widely exploited by the biotech and pharmaceutical industry. Although it is obvious that a plethora of these compounds still await discovery. Two main challenges limit the access to new compounds: i) the inability to cultivate diverse producers of natural products in the laboratory and, ii) the fact that a majority of secondary metabolite biosynthesis related genes and gene clusters are silent under standard laboratory conditions. To overcome latter obstacle several strategies including the manipulation of pleiotropic regulators of secondary metabolism are currently followed. Hence, the applicants and their teams have recently isolated and preliminarily characterized a transcription factor functioning as a pleiotropic regulator of secondary metabolite biosynthesis. First results demonstrate its striking involvement in secondary metabolite production in the filamentous fungus Trichoderma reesei and its occurrence in other biotechnologically and agriculturally relevant fungal species. Based on these results the following investigations are proposed: i) Elucidating the regulon of this trans acting factor in T. reesei; ii) Analyze the regulatory function of it in the bio-control active fungus T. atroviride the plant pathogenic fungus Fusarium graminearum and F. fujikuroi and the pharmacologically exploited fungus Claviceps purpurea, iii) Investigate the molecular mechanisms how this factor exerts it regulatory function in T. reesei

The fungal secondary metabolism is a vast, untapped source for different compounds with application potential as e.g. pharmaceuticals or pigments. Notably, most genes responsible to produce these secondary metabolites are silent under standard laboratory conditions. The project Resme aimed at developing new strategies and methods to activate these genes and to detect novel secondary metabolites. To this end, we followed a few parallel strategies. First, we studied the role and mode of function of a novel global regulator of the secondary metabolism, termed Xpp1. Next, we directly activated silent genes by a targeted overexpression approach, resulting in the discovery of two new secondary metabolites with antifungal properties. Further, we developed four new bioinformatic methods with the aim to improve the prediction and identification of SMs. Notably, Resme was also the breeding ground for several follow-up projects. We could acquire funding for 3 single research projects based on the outcomes of Resme, and started a PhD program with 10 fully-funded positions at TU Wien.