A small molecule species specifically inhibits <scp><i>F</i></scp><i>usarium</i> myosin <scp>I</scp>

Zhang, Chengqi; Chen, Yun; Yin, Yanni; Ji, Huan-Hong; Shim, Won‐Bo; Hou, Yiping; Zhou, Mingguo; Li, Xiangdong; Ma, Zhonghua

doi:10.1111/1462-2920.12711

Cited by 84 publications

(121 citation statements)

References 47 publications

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“…It has an excellent antifungal effect on Fusarium species by inhibiting the ATPase activity of their myosin class I motor domains and has a good control effect on FHB . However, previous studies have shown that F. graminearum has a medium risk of resistance to this fungicide, which phenamacril cannot be used alone . Therefore, it is important to introduce and develop new fungicides that are different from DMI and phenamacril to delay the selection of fungicide resistance and effectively control FHB in China.…”

Section: Introductionmentioning

confidence: 99%

Resistance risk assessment for Fusarium graminearum to pydiflumetofen, a new succinate dehydrogenase inhibitor

Sun

Cui

Tian

et al. 2019

Pest Management Science

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Background Pydiflumetofen is a new generation succinate dehydrogenase inhibitor currently undergoing the process of registration in China for the control of Fusarium head blight in wheat. A resistance risk assessment of Fusarium graminearum to pydiflumetofen was undertaken in this study. Results A total of 75 pydiflumetofen‐resistant mutants were generated through spontaneous selection and displayed high resistance with an average resistance factor (RF) value of 78. Four mutants were generated through UV mutagenesis and displayed very high resistance with an RF value >1000. The sequence analysis results for Sdh genes and fitness studies revealed the existence of four types of mutations. In particular, 32 spontaneous selection mutants (SP mutants) had an arginine (R) to histidine (H) transition at position 86 in FGSdhC, resulting in seriously reduced fitness. Seven SP mutants had an R to cysteine (C) transition at position 86 in FGSdhC, resulting in reduced fitness. Thirty‐six SP mutants had an alanine (A) to valine (V) transition at position 83 in FGSdhC and had no fitness penalties. The efficacy of pydiflumetofen towards a mutant carrying A83V in FGSdhC in vivo was significantly decreased at 42.7%. Four UV mutants had no mutations on all Sdh genes and no fitness penalties. Cross‐resistance among boscalid, fluopyram and pydiflumetofen was observed. Conclusion Sdhc mutations were found and other target site resistance may be present in laboratory PR mutants of F. graminearum. An overall moderate risk of resistance development in F. graminearum was recommended for pydiflumetofen. © 2019 Society of Chemical Industry

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Section: Introductionmentioning

confidence: 99%

Resistance risk assessment for Fusarium graminearum to pydiflumetofen, a new succinate dehydrogenase inhibitor

Sun

Cui

Tian

et al. 2019

Pest Management Science

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“…Point mutations in CYP51/ERG11 homologous genes (targets of azoles) in F. graminearum confers azole resistance . In our previous study, we found that a point mutation S217 L or E420K in FgMyo1 is responsible for F. graminearum resistance to phenamacril . In addition, another 11 amino acid substitutions also confer resistance to phenamacril .…”

Section: Discussionmentioning

confidence: 89%

“…In previous studies, we demonstrated that phenamacril inhibits the growth of F. graminearum by targeting the class I myosin FgMyo1 . The Pzear‐ FgMYO1 strain that conditionally expresses the essential gene FgMYO1 under the zearalenone (ZEA)‐inducible promoter (Pzear) had dramatically increased sensitivity to phenamacril in F. graminearum , when the inducer ZEA was not supplemented.…”

Section: Resultsmentioning

confidence: 99%

“…These include point mutation of FgMyo1 and up‐regulated FgMYO1 expression by FgTfmI. Mutations in the FgMyo1 resulted in high resistance to phenamacril, and were obtain with a high frequency in the laboratory screening with a high concentration of phenamacril . However, the deletion mutant ΔFgTfmI showed hypersensitivity to phenamacril (Fig.…”

Section: Discussionmentioning

confidence: 99%

“… Since 2007, it has been widely used in China for controlling FHB and rice bakanae disease caused by F. fujikuroi . Previous studies revealed that the class I myosin, FgMyoI is the drug target of phenamacril in F. graminearum . Phenamacril directly binds with FgMyo1 and suppresses the ATPase activity of FgMyo1 .…”

Section: Introductionmentioning

confidence: 99%

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The b‐ZIP transcription factor FgTfmI is required for the fungicide phenamacril tolerance and pathogenecity in Fusarium graminearum

Liu

Dawood

et al. 2019

Pest Management Science

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BACKGROUND Fusarium head blight (FHB) is a devastating disease of cereal crops worldwide mainly caused by Fusarium graminearum. Due to the unavailability of FHB‐resistant wheat cultivars, chemical fungicide application is currently the most effective approach for controlling FHB now. In the last few years, a novel cyanoacrylate fungicide, phenamacril, has been widely used in China for FHB disease management. In previous studies, we identified that myosin I (FgMyo1) is the target of phenamacril and is essential for mycotoxin deoxynivalenol (DON) biosynthesis and fungal growth. However, the regulation of FgMYO1 gene expression is still largely unknown. RESULTS In this study, we identified a b‐ZIP transcription factor, FgTfmI, which regulates the mRNA expression of FgMYO1 upon phenamacril treatment. The FgTfmI directly binds to the promoter region of FgMYO1, and is required for the upregulation of FgMYO1 in response to phenamacril treatment. The deletion mutant of FgTFMI (ΔFgTfmI) displayed a slight growth defect, while it showed hypersensitivity to phenamacril, but not to other tested fungicides. FgTfmI also contributed to DON biosynthesis and the infection process in planta. CONCLUSIONS The transcription factor FgTfmI plays an important role in regulating transcription of the genes involved in phenamacril tolerance, DON biosynthesis and virulence in F. graminearum. © 2019 Society of Chemical Industry

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(Z), Not (E) – An End to a Century of Confusion about the Double‐Bond Stereoisomers of 3‐Amino‐2‐cyanoacrylates

et al. 2017

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Potent and selective myosin inhibitors are of vast scientific interest in the development of treatments for diseases involving myosin dysfunction or overactivity. A novel fungicide, ethyl 2‐cyano‐3‐amino‐3‐phenylacrylate (commercialized as “phenamacril”), was recently identified as an inhibitor of myosin‐5 in F. graminearum. Although the compound has been known since 1900, a general confusion concerning the stereochemical configuration at the exocyclic double bond persists in the literature, thus restricting further drug development of this compound and derivatives. By using NMR and quantum mechanical calculations, this work establishes the stereoconfiguration as the (Z) form and that the effect of a single hydrogen bond is crucial in keeping these types of molecules in a single configuration.

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A small molecule species specifically inhibits Fusarium myosin I

Cited by 84 publications

References 47 publications

Resistance risk assessment for Fusarium graminearum to pydiflumetofen, a new succinate dehydrogenase inhibitor

Resistance risk assessment for Fusarium graminearum to pydiflumetofen, a new succinate dehydrogenase inhibitor

The b‐ZIP transcription factor FgTfmI is required for the fungicide phenamacril tolerance and pathogenecity in Fusarium graminearum

(Z), Not (E) – An End to a Century of Confusion about the Double‐Bond Stereoisomers of 3‐Amino‐2‐cyanoacrylates

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