Genomics-Driven Discovery of Phytotoxic Cytochalasans Involved in the Virulence of the Wheat Pathogen <i>Parastagonospora nodorum</i>

Li, Hang; Wei, Haochen; Hu, Jinyu; Lacey, Ernest; Sobolev, Alexandre N.; Stubbs, Keith A.; Solomon, Peter S.; Chooi, Yit‐Heng

doi:10.1021/acschembio.9b00791

Cited by 31 publications

(19 citation statements)

References 51 publications

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“…A series of seco-sativene sesquiterpenoids including cochliobolins A-F (269-274), drechslerines A (275) and B (276), helminthosporal acid (291), helminthosporic acid (293), helminthosporol (294), and isosativenediol (298) were isolated from Cochiliobolus sativus, the endophytic fungus isolated from a desert plant Artemisia desertorum. Among them, cochliobolin F (274), drechslerine B (276), helminthosporal acid (291), and helminthosporic acid (293) displayed strong phytotoxic effects on corn leaves by producing visible lesions [23].…”

Section: Sesquiterpenoidsmentioning

confidence: 99%

Phytotoxic Secondary Metabolites from Fungi

Xue

Shen

et al. 2021

Toxins

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Fungal phytotoxic secondary metabolites are poisonous substances to plants produced by fungi through naturally occurring biochemical reactions. These metabolites exhibit a high level of diversity in their properties, such as structures, phytotoxic activities, and modes of toxicity. They are mainly isolated from phytopathogenic fungal species in the genera of Alternaria, Botrytis, Colletotrichum, Fusarium, Helminthosporium, and Phoma. Phytotoxins are either host specific or non-host specific phytotoxins. Up to now, at least 545 fungal phytotoxic secondary metabolites, including 207 polyketides, 46 phenols and phenolic acids, 135 terpenoids, 146 nitrogen-containing metabolites, and 11 others, have been reported. Among them, aromatic polyketides and sesquiterpenoids are the main phytotoxic compounds. This review summarizes their chemical structures, sources, and phytotoxic activities. We also discuss their phytotoxic mechanisms and structure–activity relationships to lay the foundation for the future development and application of these promising metabolites as herbicides.

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Section: Sesquiterpenoidsmentioning

confidence: 99%

Phytotoxic Secondary Metabolites from Fungi

Xue

Shen

et al. 2021

Toxins

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“…11 The heterocyclic core seems to be formed by the PKS-NRPS and trans-ER alone in the cases of niduporthin 4 7 and cytochalasans from Parastagonospora nodorum. 12 The assumption that the DA reaction is not spontaneous is supported by observations in the total synthesis of cytochalasans. 13 Stork and Nakamura developed the first biomimetic macrocyclization strategy in 1982 while synthesizing cytochalasin B.…”

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confidence: 94%

Evidence for enzyme catalysed intramolecular [4+2] Diels–Alder cyclization during the biosynthesis of pyrichalasin H

2020

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Cytochalasans are highly complex fungal metabolites which exhibit diverse biological activities. Little is known of the chemical steps involved in the construction of the tricyclic core, which consists of an octahydro-isoindole skeleton fused to a macrocyclic ring. Here, using a directed gene knockout and complementation strategy, we show that PyiF is implicated as the proposed intramolecular [4+2] Diels-Alderase required for construction of the tricyclic core of pyrichalasin H 1.

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“…α,β‐Hydrolases related to PyiE and ORFZ are commonly found encoded in fungal PKS‐NRPS biosynthetic gene clusters, especially those with a reductive release mechanism [17] . For example, the cytochalasin E (CcsE), [5a] fusarin (Fus2), [18a, 24] pseurotin (PsoG), [18c] and phomacin (SnoG) [25] gene clusters all encode homologous α,β‐hydrolases. No structural data for orthologs of ORFZ/PyiE has been reported, but database (ESTHER) [26] and structural prediction (Phyre‐2, [27] Swiss‐Model) [28] searches indicate that well‐studied enzymes such as acylaminoacyl peptidase (3fnb), 2,6‐dihydroxy‐pseudo‐oxynicotine (DHPON, 2jbw) hydrolase, [29, 30] and AntI [31] (6hxa) possess the same overall protein fold.…”

Section: Resultsmentioning

confidence: 99%

Chemical and Genetic Studies on the Formation of Pyrrolones During the Biosynthesis of Cytochalasans

Zhang

Hantke

Bruhnke

et al. 2021

Chemistry A European J

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A key step during the biosynthesis of cytochalasans is a proposed Knoevenagel condensation to form the pyrrolone core, enabling the subsequent 4+2 cycloaddition reaction that results in the characteristic octahydroisoindolone motif of all cytochalasans. In this work, we investigate the role of the highly conserved α,β‐hydrolase enzymes PyiE and ORFZ during the biosynthesis of pyrichalasin H and the ACE1 metabolite, respectively, using gene knockout and complementation techniques. Using synthetic aldehyde models we demonstrate that the Knoevenagel condensation proceeds spontaneously but results in the 1,3‐dihydro‐2H‐pyrrol‐2‐one tautomer, rather than the required 1,5‐dihydro‐2H‐pyrrol‐2‐one tautomer. Taken together our results suggest that the α,β‐hydrolase enzymes are essential for first ring cyclisation, but the precise nature of the intermediates remains to be determined.

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

Abstract: actin polymerization was assessed using the Actin Polymerization Biochem assay (Cytoskeleton Inc, Denver, CO). Further experimental details of the biologial assays are provided in Supporting Information.

Cited by 31 publications

References 51 publications

Phytotoxic Secondary Metabolites from Fungi

Phytotoxic Secondary Metabolites from Fungi

Evidence for enzyme catalysed intramolecular [4+2] Diels–Alder cyclization during the biosynthesis of pyrichalasin H

Chemical and Genetic Studies on the Formation of Pyrrolones During the Biosynthesis of Cytochalasans

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