Secondary metabolism and biotrophic lifestyle in the tomato pathogen Cladosporium fulvum: from comparative genomics to reconstruction of biosynthetic pathways

A fungal biotrophic lifestyle has been associated with a reduction of the potential for production of secondary metabolites (SMs), which are in many cases toxic on the host plants. Analysis of the genome of Cladosporium fulvum, a biotrophic fungal pathogen that causes leaf mould of tomato, challenged this correlation. Indeed, C. fulvum shows a high potential for SM production, including compounds toxic on plants such as elsinochrome, with 23 core genes (10 PKSs, 10 NRPSs, 2 hybrid PKS-NRPSs and 1 DMATS) [1]. However, we showed that only two core genes, PKS6 and NPS9, show high expression in planta, but both are significantly down regulated during colonization of the mesophyll tissue [2]. This result suggests that down-regulation and low expression of SM biosynthetic pathways is another mechanism associated with biotrophy. Functional analysis of PKS6 has now confirmed this hypothesis. Comparative genomics of C. fulvum biosynthetic pathways identified two gene clusters (PKS1 and PKS6) that are conserved across Pezizomycotina. PKS1 belongs to the elsinochrome gene cluster characterized in Elsinoe fawcettii and PKS6 to the endocrocin/monodictyphenone gene cluster characterized in Aspergillus species. We are using several complementary approaches in order to determine SMs produced by these pathways in C. fulvum: i) deletion mutants; ii) over-expression of local transcription factors; iii) heterologous expression in Aspergillus oryzae. We are also determining the evolutionary history of both gene clusters in Pezizomycotina. Altogether, our recent studies suggest that some well-studied biosynthetic pathways might be conserved and ancestral, but the final compounds are diverse with different biological activities. [1] de Wit PJ, van der Burgt A, Ökmen B, Stergiopoulos I, Abd-Elsalam KA, et al., 2012. PLoS Genetics. 8(11):e1003088. [2] Collemare J, Griffiths S, Iida Y, KarimiJashni M, et al., 2014. PLoS One. 9(1):e85877.