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

dc.contributor.authorLi, Hang
dc.contributor.authorWei, Haochen
dc.contributor.authorHu, Jinyu
dc.contributor.authorLacey, E
dc.contributor.authorSobolev, Alexandre N
dc.contributor.authorStubbs, Keith A
dc.contributor.authorSolomon, Peter
dc.contributor.authorChooi, Yit-Heng
dc.date.accessioned2020-08-21T00:00:34Z
dc.date.issued2020
dc.date.updated2020-04-28T17:48:09Z
dc.description.abstractThe etiology of fungal pathogenesis of grains is critical to global food security. The large number of orphan biosynthetic gene clusters uncovered in fungal plant pathogen genome sequencing projects suggests that we have a significant knowledge gap about the secondary metabolite repertoires of these pathogens and their roles in plant pathogenesis. Cytochalasans are a family of natural products of significant interest due to their ability to bind to actin and interfere with cellular processes that involved actin polymerization; however, our understanding of their biosynthesis and biological roles remains incomplete. Here, we identified a putative polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) gene cluster (phm) that was upregulated in the pathogen Parastagonospora nodorum during its infection on wheat. Overexpression of the transcription factor gene phmR encoded in the phm gene cluster resulted in the production of two leucine-derived cytochalasans, phomacins D and E (1 and 2, respectively), and an acetonyl adduct phomacin F. Heterologous expression of the PKS-NRPS gene phmA and the trans-enoyl reductase (ER) gene phmE in Aspergillus nidulans resulted in the production of a novel 2-pyrrolidone precursor prephomacin. Reverse genetics and wheat seedling infection assays showed that ΔphmA mutants exhibited significantly reduced virulence compared to the wild type. We further demonstrated that both 1 and 2 showed potent actin polymerization-inhibitory activities and exhibited potentially monocot-specific antigerminative activities. The findings from this study have advanced our knowledge based on the biosynthesis and biological roles of cytochalasans, the latter of which could have significant implications for our understanding of the molecular mechanisms of fungus−plant interactions.en_AU
dc.description.sponsorshipThis study was funded by an Australian Research Council (ARC) Discovery Project Grant (DP170100228). Y.-H.C. is an ARC Future Fellow (FT160100233). H.L. and J.H. are supported by an Australian Government International Postgraduate Research Scholarship.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn1554-8929en_AU
dc.identifier.urihttp://hdl.handle.net/1885/207907
dc.language.isoen_AUen_AU
dc.publisherAmerican Chemical Societyen_AU
dc.relationhttp://purl.org/au-research/grants/arc/DP170100228en_AU
dc.relationhttp://purl.org/au-research/grants/arc/FT160100233en_AU
dc.rights© 2019 American Chemical Societyen_AU
dc.sourceACS chemical biologyen_AU
dc.titleGenomics-Driven Discovery of Phytotoxic Cytochalasans Involved in the Virulence of the Wheat Pathogen Parastagonospora nodorumen_AU
dc.typeJournal articleen_AU
local.bibliographicCitation.lastpage233en_AU
local.bibliographicCitation.startpage226en_AU
local.contributor.affiliationLi, Hang, The University of Western Australiaen_AU
local.contributor.affiliationWei, Haochen, College of Science, ANUen_AU
local.contributor.affiliationHu, Jinyu, University of Western Australia,en_AU
local.contributor.affiliationLacey, E, Microbial Screening Technol. Pty Ltd.en_AU
local.contributor.affiliationSobolev, Alexandre N, University of Western Australiaen_AU
local.contributor.affiliationStubbs, Keith A, University of Western Australiaen_AU
local.contributor.affiliationSolomon, Peter, College of Science, ANUen_AU
local.contributor.affiliationChooi, Yit-Heng, The University of Western Australiaen_AU
local.contributor.authoremailu4632004@anu.edu.auen_AU
local.contributor.authoruidWei, Haochen, u6030062en_AU
local.contributor.authoruidSolomon, Peter, u4632004en_AU
local.description.embargo2037-12-31
local.description.notesImported from ARIESen_AU
local.identifier.absfor060113 - Synthetic Biologyen_AU
local.identifier.absfor060704 - Plant Pathologyen_AU
local.identifier.absseo820599 - Winter Grains and Oilseeds not elsewhere classifieden_AU
local.identifier.ariespublicationu6269649xPUB392en_AU
local.identifier.citationvolume15en_AU
local.identifier.doi10.1021/acschembio.9b00791en_AU
local.identifier.scopusID2-s2.0-85077221416
local.identifier.uidSubmittedByu6269649en_AU
local.publisher.urlhttp://pubs.acs.org/journal/acbccten_AU
local.type.statusPublished Versionen_AU

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