张志民，理学博士，研究员，博士生导师。2003年6月本科毕业于中南大学材料科学与工程专业；2012年6月获得中科院上海有机化学研究所博士学位；同年赴加州大学河滨分校（UCR）从事博士后研究。2017年入职402永利集团官网生物制药系。长期以具有重要生理功能和新颖催化机制的化学修饰酶为研究对象，致力于酶的结构生物与结构药理学研究。近年来以（共）第一/通讯作者在Nature、Nature Communications、Nature Plants、Nature Structural & Molecular Biology、J. Am. Chem. Soc. 、Angew. Chem.Int. Ed.和J. Med. Chem.等国际知名期刊发表研究论文多篇。入选广东省“珠江人才”计划青年拔尖人才。

研究方向：

1、潜在药物靶标的作用机制研究

2、酶催化药物分子的生物合成机制

3、药物与靶

蛋白作用机制研究

代表性科研项目：

1、国家自然科学基金面上项目（32171184），植酸InsP6激活YopJ家族效应蛋白的分子机制研究（2022.1 -2025.12）

2、国家自然科学基金青年项目（31800638），鼠疫杆菌效应蛋白YopJ与MAPK激酶作用机制的研究（2019.1 -2021.12）

3、广东省自然科学基金面上项目（2023A1515012763），金黄色葡萄球菌伴侣蛋白EsaE介导毒蛋白转运机制研究（2023.1 -2025.12）

4、广东省自然科学基金面上项目（2022A1515012266），T7分泌系统免疫因子抑制毒蛋白活性的作用机制研究（2022.1 -2024.12）

近年主要代表性论文：

1. Ji-Qiang Jin^#, Fu-Rong Qu^#, Huisi Huang^#, Qing-Shuai Liu^#, Yuee Zhou, Zhibo Cui, Meng-Yuan Wei, Jie-Dan Chen, Wei-Dong Dai, Li Zhu, Ming-Zhe Yao*, Zhi-Min Zhang*, Liang Chen*. Identification and characterization of two O-methyltransferases involved in the biosynthesis of O-methylated catechins in tea plant. Nat. Commun.2023, 14:5075

2. Zhongtang Yu^# , Xiaoqiang He^#, Ruiliu Wang^#, Xinxin Xu, Zhang Zhang, Ke Ding*, Zhi-Min Zhang*, Yi Tan*, Zhengqiu Li*. Simultaneous Covalent Modification of K-Ras(G12D) and K-Ras(G12C) with Tunable Oxirane Electrophiles. J. Am. Chem. Soc. 2023, doi:10.1021/jacs.3c05899.

3. Peng Chen^#, Guanghui Tang^#*, Chengjun Zhu^#, Jie Sun, Xuan Wang, Menghua Xiang, Huisi Huang, Wei Wang, Lin Li, Zhi-Min Zhang*, Liqian Gao*, and Shao Q. Yao*. 2-Ethynylbenzaldehyde-Based, Lysine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Nonkinases. J. Am. Chem. Soc. 2023, 145(7): 3844-3849.

4. Zuqin Wang^#, Jie Wang^#, Yongjin Wang^#, Shuang Xiang, Hengliang Zhou, Shukai Song, Xiaojuan Song, Zhengchao Tu, Yang Zhou, Ke Ding, Zhi-Min Zhang*, Zhang Zhang* and Xiaoyun Lu*. Structure-based Optimization of the Third Generation Type II Macrocycle TRK Inhibitors with Improved Activity against Solvent-front, xDFG and Gatekeeper Mutations. J. Med. Chem. 2023, 10.1021/acs. jmedchem.3c00899

5. Peng Chen^#, Jie Sun^#, Chengjun Zhu^#, Guanghui Tang^*, Wei Wang, Manyi Xu, Menghua Xiang, ChongJing Zhang, Zhi-Min Zhang^*, Liqian Gao^*, Shao Q Yao^*. Cell-Active, Reversible, and Irreversible Covalent Inhibitors that Selectively Target the Catalytic Lysine of BCR-ABL Kinase, Angew. Chem. Int. Ed., 2022, 61(26):e202203878

6. Yongjin Wang^#, Yang Zhou^#, Guohua Lv^#, Jiacong Liu, Huisi Huang, Shengrong Li, Liping Duan, Xinyi Zheng, Yue Liu, Haibo Zhou, Zhengqiu Li, Yonghua Wang, Yun Huang, Ke Ding^*, Pinghua Sun^*, Xiaoyun Lu^*, Zhi-Min Zhang^*. A toxin-deformation dependent inhibition mechanism in the T7SS toxin-antitoxin system of Gram-positive bacteria, Nat. Commun.2022, 13: 6434.  

7. Yifan Ouyang^#, Hongfei Si^#, Chengjun Zhu^#, Liang Zhong, Haowen Ma, Zongyang Li, Xiong H, Liu Tongzheng, Liu Zhong, Zhang Zhang*, Zhi-Min Zhang*, Qian Cai*. Discovery of 8-(6-Methoxypyridin-3-yl)-1-(4-(piperazin-1-yl)-3-(trifluorometh -yl)phenyl)-1,5-dihydro-4H-[1,2,3]triazolo[4,5-c]quinolin-4-one (CQ211) as a Highly Potent and Selective RIOK2 Inhibitor. J. Med. Chem. 2022, 65 (11): 7833–7842

8. Zuqin Wang^#, Jie Wang^#, Yongjin Wang^#, Shuang Xiang, Xiaojuan Song, Zhengchao Tu, Yang Zhou, Zhi-Min Zhang^*, Zhang Zhang^*, Ke Ding^*, Xiaoyun Lu^*. Discovery of the First Highly Selective and Broadly Effective Macrocycle-Based Type II TRK Inhibitors that Overcome Clinically Acquired Resistance, J. Med. Chem., 2022, doi:10.1021/acs.jmedchem.2c00308

9. Yao Xia^#, Rongfeng Zou^#, Maxime Escouboué^#, Liang Zhong^#, Chengjun Zhu, Cécile Pouzet, Xueqiang Wu, Yongjin Wang, Guohua Lv, Haibo Zhou, Pinghua Sun^*, Ke Ding^*, Laurent Deslandes^*, Shuguang Yuan^*, Zhi-Min Zhang^*. Secondary-structure switch regulates the substrate binding of a YopJ family acetyltransferase, Nat. Commun., 2021, 12: 5969.

10. Zexing Wen^#, Zhi-Min Zhang^#, Liang Zhong^#, Jiaqian Fan, Min Li, Yuanhong Ma, Yang Zhou, Wei Zhang, Bin Guo, Bo Chen, and Jian-Bo Wang. Directed Evolution of a Plant Glycosyltransferase for Chemo- and Regioselective Glycosylation of Pharmaceutically Significant Flavonoids, ACS Catalysis, 2021, doi: 10.1021/acscatal. 1c04191

11. Youlong Fan^#, Hongfei Si^#, Zhang Zhang, Liang Zhong, Hongyan Sun, Chengjun Zhu, Zhibin Yin, Huilin Li, Guanghui Tang, Shao Q Yao, Pinghua Sun^*, Zhi-Min Zhang^*, Ke Ding^*, Zhengqiu Li^*. Novel Electrophilic Warhead Targeting a Triple-Negative Breast Cancer Driver in Live Cells Revealed by "Inverse Drug Discovery, J. Med. Chem., 2021, doi: 10.1021/acs.jmedchem.0c02024

12. Yue-Hong Zhang^#, Yi-Fang Li^#, Yongjin Wang^#, Li Tan, Zhi-Qin Cao, Chao Xie, Guo Xie, Hai-Biao Gong, Wan-Yang Sun, Shu-Hua Ouyang, Wen-Jun Duan, Xiao yun Lu, Ke Ding, Hiroshi Kurihara, Dan Hu*, Zhi-Min Zhang*, Ikuro Abe*, and Rong-Rong He*. Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea，Nat. Commun., 2020, 11: 1473.

13. Zhi-Min Zhang^#, Rui Lu^#, Pengcheng Wang, Yang Yu, Dongliang Chen, Linfeng Gao, Shuo Liu, Debin Ji, Scott B. Rothbart, Yinsheng Wang, Gang Greg Wang*&Jikui Song*. Structural basis for DNMT3A-mediated de novo DNA methylation, Nature, 2018, 554(7692): 387-391

14. Zhi-Min Zhang^#, Ka-Wai Ma^#, Linfeng Gao^#, Zhenquan Hu, Simon Schwizer, Wenbo Ma*, and Jikui Song*. Mechanism of Host Substrate Acetylation by a Yopj Family Effector. Nat. Plants, 2017, 3:17115.

15. Zhi-Min Zhang^#, Ka-Wai Ma^#, Shuguang Yuan, Youfu Luo, Shushu Jiang, Eva Hawara, Songqin Pan, Wenbo Ma*, Jikui Song*. Structure of a pathogen effector reveals enzymatic mechanism of a novel acetyltransferase family, Nat. Struct & Mol. Biol., 2016, 23(9):847-852.