Fungal natural products for food safety: towards biocontrol of cereal blast diseases by disrupting the novel target septins.

Projektbeschreibung

Pilzliche Naturprodukte gegen neuartige antimykotische Ziel-Septine

Die globale Ernährungssicherheit ist durch die Ausbreitung von Pilzkrankheiten ständig bedroht, ein Risiko, das durch den Klimawandel nur noch verstärkt wird. Das Auftreten von pathogenen Pilzstämmen, die gegen viele gebräuchliche Fungizide resistent sind, erfordert nachhaltige und robuste Methoden zur Krankheitsbekämpfung. Das über die Marie-Skłodowska-Curie-Maßnahmen unterstützte Projekt TargetSep wird natürliche Pilzprodukte erforschen, die Septine hemmen – Proteine, die für die Fähigkeit eines Pilzes, in Wirtspflanzen einzudringen und sie zu infizieren, unerlässlich sind. Da diese Proteine in Pflanzen selbst nicht vorkommen, könnten Septine ideal für die Entwicklung von Antimykotika geeignet sein. Die Forschenden werden mithilfe eines synthetisch-biologischen Ansatzes Kandidaten für Pilzverbindungen identifizieren, deren Aktivität gegen Septine in vitro und in planta testen und ihre Struktur charakterisieren. Diese Arbeit könnte zu umweltfreundlichen Strategien der biologischen Schädlingsbekämpfung führen, um die zukünftige Getreideproduktion zu sichern.

Ziel

A consequence of climate change is the emergence of fungal plant diseases in Europe. Blast disease on cereal crops is an economically important plant disease caused by the fungus Pyricularia oryzae and poses a significant threat to global food security. While initially well known as the major disease on rice, wheat blast has recently emerged and is of major concern in wheat production areas since P. oryzae has already developed resistance against most used fungicides. Sustainable solutions for the biocontrol of the cereal blast disease are needed, and active fungal natural products inhibiting novel targets represent a promising alternative.
Septin proteins are essential for the pathogenicity of P. oryzae and other fungal plant pathogens and their absence in land plants makes them compelling targets. Yet, no product has been developed to target fungal septins. In a preliminary study, we employed a self-resistance guided genome mining approach to identify candidate biosynthetic pathways of fungal natural products which contain a septin decoy gene. Two biosynthetic pathways were found to likely produce septin-disrupting compounds. I propose to investigate these candidate pathways and validate their potential to control cereal blast. First, wild fungal species containing the identified pathways will be tested for septin-disrupting activity using in vitro fluorescence microscopy-based assay. Second, a synthetic biology approach to activate these candidate pathways in the heterologous host Aspergillus oryzae will aid in characterizing natural compounds and their structure-activity relationships. Finally, natural septin-disrupting compounds will be tested for their ability and efficacy to control blast disease in planta. During TargetSep, I will embark on a multidisciplinary journey to discover natural solutions to control a disease that threatens food safety, while developing various skills like leadership and science communication to fulfill my scientific pursuits.