生物技术药物学系

李子宁 博士 (特聘副研究员)

来源:综合事务办 发布时间:2024年04月23日 点击数:

基本概况

单位:四川大学华西药学院生物技术药物学系


地址:成都市武侯区人民南路三段17号华西药学院

邮编:610041

电子邮箱: ziningli@scu.edu.cn

李子宁,理学博士,四川大学华西药学院特聘副研究员。为解决天然产物的发现与合成等方面的科学问题,李子宁博士以天然产物(药物)为中心开展了广泛交叉且深入的研究工作。研究内容涵盖天然产物紧密相关的三个领域,包括:(1)发现新颖的天然产物并解析生物合成途径;(2)鉴定新型生物酶及解析其催化机制;(3)天然产物的全合成。迄今为止,发现了4个结构新颖的二萜天然产物,其中包括3个反式6/10-eunicellane型天然产物albireticulene、iso-albireticulene和albireticulone A以及罕见的萜类阻转异构体albiretol;在此基础上全面解析了首个反式eunicellane萜类合酶AlbS,和鉴定了隐秘的异构化酶AlbU和P450氧化酶AlbP1,还创造性地修复了P450氧化酶AlbP2*,阐明了该家族相关天然产物的生物合成途径。此外,基于汇集式合成策略,利用Staudinger还原反应,在是否有水参与的条件下,控制不同的环化过程来实现不同环系骨架的选择性构建,完成了天然产物mersicarpine、leuconodine B、melodinine E、leuconoxine和leuconolam等5个单萜吲哚生物碱天然产物的全合成。

教育与工作经历

2024.03至今四川大学华西药学院特聘副研究员

2019.08—2024.01 美国佛罗里达大学博士后

合作导师:Jeffrey D. Rudolf教授.

2019.01—2019.07北京大学助理研究员,合作导师:余志祥教授

2016.07—2018.12北京大学博士后,合作导师:余志祥教授

2010.09—2016.06南开大学元素有机国家重点实验室(SKLEOC)

有机化学理学博士,导师:梁广鑫教授

2006.09—2010.06东北林业大学学士学位

荣誉与奖励

2015元素有机所第二届EOC会议优秀墙报奖

2015光华奖学金

2014南开大学化学科学与工程研究生创新中心奖学金

2014 南开大学万香奖学金

2013 南开大学万香奖学金

2012 南开大学万香奖学金

研究兴趣:

1.微生物基因组挖掘发现新的天然产物

2.新型酶催化剂的发现与催化机制解析,开发与应用于天然产物(药物)的合成

3.利用合成生物学生产高附加值化合物和生物活性天然产物(药物)

主持的科研项目:

1.四川大学引进人才启动经费,2024-2027

已发表的工作:

1.Cryptic isomerization in diterpene biosynthesis and the restoration of an evolutionarily defunct P450.Zining Li, Baofu Xu, Tyler Alsup, Xiuting Wei, Wenbo Ning, Daniel Icenhour, Michelle Ehrenberger, Ion Ghiviriga, Bao-Doan Giang, Jeffrey Rudolf*.J. Am. Chem. Soc.2023,145, 22361–22365.

2.First trans-eunicellane terpene synthase in bacteria.Zining Li, Baofu Xu, Volga Kojasoy, Teresa Ortega, Donovon A. Adpressa, Wenbo Ning, Xiuting Wei, Jamin Liu, Dean J. Tantillo, Sandra Loesgen, Jeffrey D. Rudolf*.Chem,2023,9, 698–708.

3.Biosynthesis, enzymology, and future of eunicellane diterpenoids.Zining Li, Jeffrey D. Rudolf*.J. Ind. Microbiol. Biotechnol.,2023,50,kuad027.

4.Selective syntheses of leuconolam, leuconoxine, and mersicarpine alkaloids from a common intermediate through regiocontrolled cyclizations by Staudinger reactions.Zining Li, Qian Geng, Zhe Lv, Beau P. Pritchett, Katsuaki Baba, Yoshitaka Numajiri, Brian M. Stoltz* and Guangxin Liang*,Org. Chem. Front.,2015,2, 236–240.

5.TfOH and HBF4Mediated Formal Cycloisomerizations and [4+3] Cycloadditions of Allene-Alkynylbenzenes. Yu Xiang,Zining Li, Lu-Ning Wang, Zhi-Xiang Yu*.J. Org. Chem.2018,83, 7633–7647. (Contributed equally)

6.Quick access to the core of mersicarpine through an SNAr strategy.Zining Liand Guangxin Liang*,Tetrahedron Lett.2013,54,242–244.

7.Cytochrome P450-Mediated Cyclization in Eunicellane-Derived Diterpenoid Biosynthesis. Zengyuan Wang, Qian Yang*, Jingyi He, Haixin Li, Xingming Pan,Zining Li, Hui-Min Xu, Jeffrey D. Rudolf, Dean J. Tantillo and Liao-Bin Dong*.Angew. Chem., Int. Ed.,2023, e202312490.

8.Bacterial Diterpene Synthases Prenylate Small Molecules.Baofu Xu,Zining Li, Tyler A. Alsup, Michelle A. Ehrenberger, Jeffrey D. Rudolf*.ACS Catal.2021, 11, 5906–5915.

9.Bacterial terpenome. Jeffrey D. Rudolf*, Tyler A. Alsup, Baofu Xu andZining Li. Nat. Prod. Rep.,2021, 38,905-980.

10.Rapid Construction of the Common [5–5–6] Tricyclic Ring Skeleton in Polycyclic Cembranoids and Norcembranoids via Intramolecular 1,3-Dipolar Cycloaddition. Meng Deng, Xiao Zhang,Zining Li, Hongbin Chen, Shaoli Zang, Guangxin Liang*.Org. Lett.2019,21, 1493–1496.

11.Progress in Total Syntheses of Leuconolam-Leuconoxine-Mersicarpine Alkaloids. Qian Geng,Zining Li, Zhe Lv, Guangxin, Liang*,Chin. J. Org. Chem.2016,36, 1447–1464.

12.Total synthesis of mersicarpine through a cationic cyclization approach. Zhe Lv,Zining Liand Guangxin Liang*,Org. Lett.2014,16,1653–1655.

13.Early-Stage Biosynthesis of Phenalinolactone Diterpenoids Involves Sequential Prenylation, Epoxidation, and Cyclization. Tyler A. Alsup,Zining Li, Caitlin A. McCadden, Annika Jagels, Diana Łomowska-Keehner, Erin Marshall, Liao-Bin Dong, Sandra Loesgen, Jeffrey D. Rudolf*.https://doi.org/10.26434/chemrxiv-2024-5fbcg. (submitted)