Fungal plant pathogens as a source of novel herbicides – HerbiFun

The search for natural products with novel herbicidal activities is of great importance for agriculture, since most existing herbicides are either banned or inefficient due to resistant weeds, and the flow of novel herbicides identified by classical chemical screening is dramatically reduced. Plant pathogenic fungi are a potential source of novel natural products-based herbicides because they produce Secondary Metabolites (SMs) during infection that either inhibit plant pathways and/or are toxic to plant cells. Recently, the genomes of these fungi revealed huge repertoires of genes dedicated to the biosynthesis of SMs. However, these repertoires of natural compounds remain under-explored, mainly because they are only produced during interaction with host plants (infection-specific expression patterns).
The aim of HerbiFun is to exploit fungal genomes and their regulatory networks to produce infection-specific fungal SMs in vitro and discover bioactive SMs that could be used as novel natural herbicides. Bioinformatic tools will be used to fully characterize the genes involved in fungal SM biosynthesis including regulatory genes (pathway-specific transcription factors) in four plant pathogenic species with distinct host ranges and SM repertoires: (1) Botrytis cinerea (Leotiomycetes), a necrotrophic pathogen with a very broad host range among dicot plants (>200 species) causing pre- and postharvest crop losses worldwide, (2) the hemibiotrophic Colletotrichum higginsianum (Sordariomycetes) which attacks many cultivated members of the Brassicaceae as well as the model plant Arabidopsis thaliana, (3) the hemibiotrophic Zymoseptoria tritici (Dothideomycetes) which causes the most important foliar disease in wheat (the “Septoria tritici blotch”) and (4) Magnaporthe oryzae (Sordariomycetes), also a hemibiotroph, responsible for rice blast, the most important fungal disease of rice worldwide. The expression of SM genes will be induced in vitro using complementary strategies based on over-expression of pathway-specific transcription factors, and the manipulation of chromatin modifiers acting as global regulators of SM gene expression (deletion of genes encoding repressors such as Histone Methyl Transferases, overexpression of the LAE activator). Finally, state-of-the-art techniques will be used to extract and purify the metabolites produced by these genetically modified fungal strains using large-scale cultures. The chemical structure of these metabolites will be determined using state-of-the-art equipment from ICSN, an internationally recognized natural products chemistry Institute. We anticipate obtaining a total of thirty to forty fungal SMs that are normally produced only during plant infection, in quantities sufficient for biological assays. These fungal SMs will be tested for their herbicidal activities using biological assays on model plants and weeds of agronomic importance. Fungal SMs with phytotoxic activity or inhibiting specific functions of the plant cell will be further characterized for their mode of action, and their ability to control weeds in glasshouse.
The HerbiFun project is consistent with the aims of the Challenge 5 “Food security and demographic challenge” and to its Axe 5 “Bioeconomy: from production to diversified uses of biomass”. It includes three academic partners with expertise in Bioinformatics (I2BC, Université d’Orsay), Fungal genomics (BIOGER, INRA, Grignon) and Chemistry of natural products (ICSN, CNRS, Gif) as well as a biopesticides company (De Sangosse).