Inhibition of chitin deacetylases to attenuate plant fungal diseases

Lin Liu; Yeqiang Xia; Yingchen Li; Yong Zhou; Xiaofeng Su; Xiaojing Yan; Yan Wang; Wende Liu; Hongmei Cheng; Yuanchao Wang; Qing Yang

doi:10.1038/s41467-023-39562-7

Inhibition of chitin deacetylases to attenuate plant fungal diseases

Nat Commun. 2023 Jun 29;14(1):3857. doi: 10.1038/s41467-023-39562-7.

Authors

Lin Liu^#^{1

2

3}, Yeqiang Xia^#^{4

5

6}, Yingchen Li^#³, Yong Zhou⁷, Xiaofeng Su⁸, Xiaojing Yan³, Yan Wang^{4

5

6}, Wende Liu³, Hongmei Cheng⁹, Yuanchao Wang^{10

11

12}, Qing Yang^{13

14

15}

Affiliations

¹ School of Bioengineering, Dalian University of Technology, 116024, Dalian, China.
² Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, 518000, Shenzhen, China.
³ State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, 100193, Beijing, China.
⁴ Department of Plant Pathology, Nanjing Agricultural University, 210095, Nanjing, China.
⁵ Key Laboratory of Soybean Disease and Pest Control (Ministry of Agriculture and Rural Affairs), Nanjing Agricultural University, 210095, Nanjing, China.
⁶ The Key Laboratory of Plant Immunity, Nanjing Agricultural University, 210095, Nanjing, China.
⁷ School of Software, Dalian University of Technology, 116024, Dalian, China.
⁸ Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
⁹ Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China. chenghongmei@caas.cn.
¹⁰ Department of Plant Pathology, Nanjing Agricultural University, 210095, Nanjing, China. wangyc@njau.edu.cn.
¹¹ Key Laboratory of Soybean Disease and Pest Control (Ministry of Agriculture and Rural Affairs), Nanjing Agricultural University, 210095, Nanjing, China. wangyc@njau.edu.cn.
¹² The Key Laboratory of Plant Immunity, Nanjing Agricultural University, 210095, Nanjing, China. wangyc@njau.edu.cn.
¹³ School of Bioengineering, Dalian University of Technology, 116024, Dalian, China. qingyang@caas.cn.
¹⁴ Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, 518000, Shenzhen, China. qingyang@caas.cn.
¹⁵ State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, 100193, Beijing, China. qingyang@caas.cn.

^# Contributed equally.

Abstract

Phytopathogenic fungi secrete chitin deacetylase (CDA) to escape the host's immunological defense during infection. Here, we showed that the deacetylation activity of CDA toward chitin is essential for fungal virulence. Five crystal structures of two representative and phylogenetically distant phytopathogenic fungal CDAs, VdPDA1 from Verticillium dahliae and Pst_13661 from Puccinia striiformis f. sp. tritici, were obtained in ligand-free and inhibitor-bound forms. These structures suggested that both CDAs have an identical substrate-binding pocket and an Asp-His-His triad for coordinating a transition metal ion. Based on the structural identities, four compounds with a benzohydroxamic acid (BHA) moiety were obtained as phytopathogenic fungal CDA inhibitors. BHA exhibited high effectiveness in attenuating fungal diseases in wheat, soybean, and cotton. Our findings revealed that phytopathogenic fungal CDAs share common structural features, and provided BHA as a lead compound for the design of CDA inhibitors aimed at attenuating crop fungal diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases
Chitin
Cladribine
Cytidine Deaminase
Humans
Inhibition, Psychological*
Mycoses*

Substances

chitin deacetylase
Amidohydrolases
Chitin
Cladribine
Cytidine Deaminase