Lae1-regulation of secondary metabolism in Trichoderma

Secondary metabolism is a term for pathways and products of metabolism that have been believed for a long time not to be absolutely required for the survival of the organism, such as antibiotics, growth stimulants, flavors and pigments. They are produced by microbes, plants and animals, but filamentous fungi are unique in producing a particularly wide range of secondary metabolites. Most secondary metabolites are produced after the fungus has completed its initial growth phase and is beginning a stage of development represented by the formation of spores. Their regulation by both nutritional as well as developmental conditions has been established and includes carbon, nitrogen and phosphorous availability, as well as partial correlation with conidiogenesis. More recently, an important further insight into the regulation of secondary metabolite synthesis was contributed by identification of the methyltransferase LaeA as a transcriptional regulator of secondary metabolite gene clusters, but the respective work has been limited to investigations of members of the genus Aspergillus. Fungi belonging to the genus Hypocrea/Trichoderma are among the fungi with most diverse impact on mankind: the soil fungus H. jecorina (T. reesei) is widely used for the production of cellulolytic and hemicellulolytic enzymes and recombinant proteins. Yet other species such as T. harzianum., T. asperellum, H. virens and H. atroviridis are potent mycoparasites and used as biological control agents against various plant diseases. This mycoparasitic attack of Hypocrea/Trichoderma spp. is a complex process, consisting of several successive steps including formation of secondary metabolites. In addition, secondary metabolites have recently been shown to be able to enhance root and plant growth and to induce systemic and localized resistance in plants. A better knowledge of how Hypocrea?Trichoderma spp. interact with their environment may be crucially important for agricultural uses and for understanding the roles of Hypocrea?Trichoderma in natural and managed ecosystems. Finally, some Trichoderma spp. also have negative impacts on mankind such as T. longibrachiatum and H. orientalis, which can infect immunocompromised humans and animals. Trichoderma spp. produce an impressing list of secondary metabolites (Sivasithamparam and Ghisalberti 1998), but the role of these components in their interaction with their environment is not known. In this project, we wish to test two hypotheses: first, that the Trichoderma Lae1 orthologue indeed fulfills a similar function in Trichoderma as in Aspergillus. And second, anticipating that the first hypothesis is correct, we will use LaeA-loss of function mutants to study the role of secondary metabolite synthesis in Trichoderma with respect its mycoparasitic action against other fungi; its action as an elicitor of plant resistance; and its action as a facultative human pathogen. In addition n, we will also investigate the signalling pathways controlling the function of LaeA in Trichoderma, and thus leading to secondary metabolite synthesis.

The Aspergillus nidulans LaeA protein, a putative S-adenosylmethionine-dependent protein methyltransferase, was originally described as a global regulator of secondary metabolism and later shown to be required for the biosynthesis of secondary metabolites in fungi in general. In this project, we could show that in two species of the fungal genus Trichoderma, LAE1 also regulates the expression of genes encoding cellulases and hemicellulases, and that it is involved in mechanisms of recognition, defense and combating other fungi. These both properties expand the roles of LaeA/LAE1 in general and are also important for strain improvement in the biofuel/biorefinery and biocontrol industry. In addition, we show that LAE1 controls asexual development, and influences the expression of genes related to environmental fitness. We conclude that in Trichoderma, LAE1 regulates those processes that are related to the specialization of the fungus in its ecological niche.