Genomics-Driven Discovery of Phytotoxic Cytochalasans Involved in the Virulence of the Wheat Pathogen Parastagonospora nodorum
Date
2020
Authors
Li, Hang
Wei, Haochen
Hu, Jinyu
Lacey, E
Sobolev, Alexandre N
Stubbs, Keith A
Solomon, Peter
Chooi, Yit-Heng
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American Chemical Society
Abstract
The 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.
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ACS chemical biology
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Journal article
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2037-12-31
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