Genomics-Driven Discovery of Phytotoxic Cytochalasans Involved in the Virulence of the Wheat Pathogen Parastagonospora nodorum

• DOI: 10.1021/acschembio.9b00791
• Publication Date: 2019-12-09T19:47:53Z
• Authors: Hang Li; Haochen Wei; Jinyu Hu; Ernest Lacey; Alexandre N. Sobolev; Keith A. Stubbs; Peter S. Solomon; Yit-Heng Chooi
• Keywords: Nonribosomal peptide; Gene cluster; Aspergillus nidulans; Polyketide synthase; Heterologous expression; Secondary metabolite

The etiology of fungal pathogenesis grains is critical to global food security. large number orphan biosynthetic gene clusters uncovered in plant pathogen genome sequencing projects suggests that we have a significant knowledge gap about the secondary metabolite repertoires these pathogens and their roles pathogenesis. Cytochalasans are family natural products interest due ability bind actin interfere with cellular processes involved polymerization; however, our understanding biosynthesis biological remains incomplete. Here, identified putative polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) cluster (phm) was upregulated Parastagonospora nodorum during its infection on wheat. Overexpression transcription factor phmR encoded phm resulted production two leucine-derived cytochalasans, phomacins D E (1 2, respectively), an acetonyl adduct phomacin F. Heterologous expression PKS-NRPS phmA trans-enoyl reductase (ER) phmE Aspergillus nidulans novel 2-pyrrolidone precursor prephomacin. Reverse genetics wheat seedling assays showed ΔphmA mutants exhibited significantly reduced virulence compared wild type. We further demonstrated both 1 2 potent polymerization-inhibitory activities potentially monocot-specific antigerminative activities. findings from this study advanced based latter which could implications for molecular mechanisms fungus–plant interactions.