Break the 50-year bottleneck!The first "Nature" paper in the history of China's pesticide field was published

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▎WuXi AppTec Content Team Editor

To understand the significance of this research, start with chitin.Chitin, commonly known as chitin, is the most abundant aminoglycan on earth.Although the name may be unfamiliar, chitin is quite common in nature: Chitin is an integral component of structures such as the shells of insects and the cell walls of fungi; but at the same time,This substance does not exist in plants and mammals.

For scientists, such characteristics make chitin an excellent material for pesticide research and development.If we can design pesticides for chitin synthase to inhibit the synthesis of chitin by pests and pathogenic fungi, it can play the role of fungicides and insecticides; at the same time, the human body does not contain chitin, so this type of pesticide is safe for the human bodyharmless.

As early as half a century ago, scientists developed drugs that inhibit the synthesis of chitin in fungi or insects, and related pesticides have appeared on the market.However, for a long time, the research and development of such pesticides has been slow and the types of pesticides are single. A key obstacle is the lack of accurate information on the three-dimensional structure of chitin synthase, which leads to the unclear structure-function relationship of chitin synthase., which hinders the design of pesticides.

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▲Soybeans infected with Phytophthora sojae (Photo credits: Vanessa Tremblay, Debra L. McLaren, Yong Min Kim, Stephen E.Strelkov, Robert L. Conner, Owen Wally, and Richard R. Bélanger)

In this latest study, the research team successfully deciphered the biosynthesis of chitin by means of cryo-electron microscopy, scanning electron microscopy, and X-ray diffraction.The research object they selected was the chitin synthase PsChs1 of Phytophthora sojae (Phytophthora sojae).Phytophthora sojae can cause rhizome rot in soybeans, causing economic losses in excess of $1 billion a year.

The research team analyzed the three-dimensional structure of PsChs1 in 5 different states, including: free state, and substrate (N-acetylglucose)amine) binding, binding to chitin oligomers, binding to products after the reaction, and binding to synthase inhibitors (nickymycin).Based on the structures in these different states, the research team elucidated the complete process of chitin biosynthesis and revealed the mechanism by which nicomycin inhibits chitin biosynthesis.

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▲PsChs1 three-dimensional structure and chitin synthesis mechanism (Image source: Reference [1]; Institute of Plant Protection, Chinese Academy of Agricultural Sciences)

These structures reveal substrate binding sites, catalytic centers, and access to transmembrane transport channels in the chitin synthesis reaction chamber, reflecting chitin biosynthesisKey steps: PsChs1 binds to the substrate, the newly generated chitin chain is extended, and the product is released to the outside of the cell through the transmembrane transport channel.

This is the first time scientists have demonstrated a directional, multi-step coupled chitin biosynthesis process at the atomic level and provide a structural basis for inhibiting this process.In summary, this work provides basic and key information for the development of green pesticides targeting chitin synthesis.

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▲Nicomycin inhibits chitin biosynthesis (Image source: Reference [1])

As for the significance of this breakthrough, Qian Xuhong, academician of the Chinese Academy of Engineering and president of East China Normal University, commented that this research has broken through the development bottleneck in the field of chitin pesticides for nearly 50 years.Through the analysis of the binding mode of chitin synthase with substrates, products and inhibitors at the atomic scale, we provide a stage for the realization of the dream of eco-friendly pesticides that has not been realized for decades:Precise design of green pesticides based on the structure of chitin synthase.

Professor Yang Qing said that it may take 10 years or more from research to production application.Next, on the one hand, they will carry out in-depth research on the molecular design of chitin synthase inhibitors for a variety of important pathogens and major pests; in addition, they will also evaluate the field control efficacy and safety of these chitin synthase inhibitors through field experiments.

References:

[1] Chen, W., Cao, P., Liu, Y. et al. Structural basis for directional chitin biosynthesis. Nature (2022).

[2] My scientist deciphers the mechanism of chitin biosynthesis to speed up the original innovation of green pesticides. Retrieved Sep. 22, 2022

[3] 15 years!This ancient biosynthesis mystery solved. Retrieved Sep. 22, 2022

Original title: Break the 50-year bottleneck!The first "Nature" in the history of China's pesticide field, deciphering the mechanism of chitin biosynthesis

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