李德海

作者：蔡超时间：2019-09-03

李德海

博士

教授

博士生导师

科室：

海洋天然药物化学

办公电话：

0532-82031826

电子邮箱：

dehaili@ouc.edu.cn

联系地址：

山东省青岛市鱼山路5号中国海洋大学医药学院地质馆225

研究方向：

主要从事海洋天然药物化学研究。主要包括：

1. 深远海、海洋动植物共附生等微生物的分离及功能基因挖掘利用；

2. 海洋微生物药物先导化合物的发现、结构优化及构效关系研究；

3. 海洋来源真菌次级代谢产物的生物合成。

个人简介

李德海，男，博士，中国海洋大学“筑峰”三层次教授、博导；海洋药物教育部重点实验室常务副主任；医药学院副院长。国际期刊Mar. Drugs、Curr. Org. Chem编辑；应用海洋学学报（中文核心期刊）第六届编委会委员。主要从事海洋天然药物化学研究，致力于利用化学和生物学手段从海洋微生物中发现具有潜在药用价值的活性成分。多年来在J Am Chem Soc、Angew. Chem. Int. Ed.、Nat. Commun.、Chem. Sci.、Adv. Sci.、J Med Chem、Org Lett、J Nat Prod等期刊SCI收录论文160余篇，个人H指数50，i10指数155（Google Scholar数据）；获授权专利10余项。主持承担国家自然科学基金、山东省、教育部等二十余个项目。

教育背景

2002.09~2007.06

中国海洋大学

药物化学

博士

1998.09~2002.06

山东大学

药学

学士

工作经历

2014.08~2015.08

Universityof California, Los Angeles(Yi Tang group)

访问学者

2014.01~至今

中国海洋大学医药学院

教授

2009.10~2013.12

中国海洋大学医药学院

副教授

2007.07~2009.07

University of British Columbia, (Raymond Andersen group)

博士后

学术兼职

山东省人民政府学位委员会第一届专业学位研究生教育指导委员会委员；中国微生物学会普通微生物专业委员会委员、中国药学会高级会员、中国海洋湖沼学会药学分会理事、山东省药学会药物化学专业委员会常务委员、青岛市药学会中药与天然药物专业委员会常务委员、青岛市归国华侨联合会新侨创新创业青岛联盟理事。

荣誉奖励

教育部“新世纪优秀人才支持计划”（2012年）、“山东省自然科学杰出青年基金”（2014年）获得者，入选青岛海洋科学与技术国家实验室“鳌山人才”优秀青年学者（2015年）、山东省“泰山学者”（2018年青年专家、2024年特聘专家）、教育部“****”青年专家（2019年）、自然资源部“高层次科技创新人才”（第三梯队）（2019年）。被评为获第九届青岛市青年科技奖（2013年）、国家海洋局优秀科技青年（2015年）、美国化学会会员奖（ACS Membership Award）（2015年）、山东省自然科学学术创新奖（2016年）、中国药学会以岭生物医药奖（2018年）海南省自然科学奖二等奖（2024年）。

承担课程

药物化学（本科生课程）

天然有机化合物结构解析（研究生课程）

海洋天然药物化学（Marine Natural Products Chemistry，研究生英文课程）

研究进展

以海洋微生物活性代谢产物发现为核心，利用多学科高度交叉的前沿技术探索海洋微生物的功能基因、活性分子及其潜在的药用价值。(1)开拓了深海药用微生物新资源、挖掘了菌株沉默基因资源，提高了海洋生物资源的利用效率：深海微生物研究少、潜力大，是亟待开发的药用新资源。发挥依托单位在海洋学科的优势，获得了200余份千米以下深海样品；针对深海微生物培养难的问题不断探索，获得了1500余株真菌和放线菌。并针对海洋微生物大多数活性分子的编码基因处于沉默状态的问题，融合“OSMAC策略”、“表观遗传修饰”、“基因组采掘”等新技术形成了“基因-化学-活性”相结合的海洋微生物挖掘利用研究模式，激活产生了近百个新型活性代谢产物。（2）阐明了多个海洋复杂分子的精确结构、潜在药用价值和生物合成机制：针对天然产物结构确定难度大的挑战，利用量子化学计算等新技术，精确鉴定了300余个结构新颖的化合物（包括20余种新骨架），其中100余个具有抗肿瘤等生物活性。鉴于新颖的结构和显著的生物活性，近年来所发现的Penicitol A等11个分子被权威评论性期刊Nat. Prod. Rep.评为“热点化合物” (Hot off the press)。

代表性成果

代表性论文(*通讯作者；+共同一作)

1. Kaijin Zhang#, Jingxian Sun#, Wencai Song, Junyu Liu, Chuanteng Ma, Yinghan Chen, Yan Guan, Yuting Liu, Zilin Ren, Qian Che, Guojian Zhang, Yankai Liu, Tianjiao Zhu, Dehai Li*. Multifunctional Cytochrome P450 Orchestrates Radical Cleavage and Non-radical Cyclization in 5-Oxaindolizidine Biosynthesis. Chem. Sci., 2025, DOI: 10.1039/D4SC07174C

2. Falei Zhang#, Chuanteng Ma#, Meilin Zhu#, Yinghan Chen, Wenxue Wang, Guojian Zhang, Tianjiao Zhu, Qian Che, Dehai Li*. Biosynthesis of Dothideomins Reveals a Fungal P450 That Constructs the Tricyclo[5.2.2.0.4,8]undecane-Imbedded Core Skeleton. J. Am. Chem. Soc. 2025, 147, 8, 7094–7102

3. Yongchun Zhu#, Xianyan Zhang#, Chuanteng Ma, Xingtao Ren, Wenxue Wang, Kaijin Zhang, Guojian Zhang, Qian Che, Tianjiao Zhu, Dehai Li*. Discovery and Characterization of a Fungal N-acetylglucosamine Transferase in the Biosynthesis of Furanone Glycosides. J. Nat. Prod.2025,88, 2, 427–432

4. Xiaofei Huang#, Xiao Xu#, Luning Zhou, Chuanteng Ma, Wenxue Wang, Chen Li, Jiaxiang Wang, Guojian Zhang, Dehai Li*, Qian Che*, Tianjiao Zhu*. Naphpyrones A–H, Antibacterial Aromatic Polyketides Isolated from the Streptomyces coelicolor A3(2)/spi1 ΔspiH3. J. Agric. Food Chem.2024, 73, 1, 541–548

5. Wenxue Wang#, Peng Wang#, Chuanteng Ma#, Kang Li#, Zian Wang, Yuting Liu, Lu Wang, Guojian Zhang, Qian Che, Tianjiao Zhu, Yuzhong Zhang*, Dehai Li*. Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines. Nat. Commun. 2025, 16, 144, doi: https://doi.org/10.1038/s41467-024-55537-8

6. Jilong Li, Zhen Mo, Longchun Liu, Shuai Tian, Yu Tang*, Dehai Li*. Total synthesis of (-)-ilicicolin H. Tetrahedron Lett. 2024, 142, 6, 155095-155098

7. Xiao Xu, Yimin Chang, Yinghan Chen, Luning Zhou, Falei Zhang, Chuanteng Ma, Qian Che, Tianjiao Zhu, Blaine A. Pfeifer, Guojian Zhang*, and Dehai Li*. Biosynthesis of Atypical Angucyclines Unveils New Ring Rearrangement Reactions Catalyzed by Flavoprotein Monooxygenases. Org. Lett.2024, 26, 36, 7489–7494

8. Hang Yu, Rui Feng, Fenglin Chen, Zuodong Wu, Dehai Li*, Xue Qiu*. Rapid FRET Assay for the Early Detection of Alpha-Synuclein Aggregation in Parkinson’s Disease. ACS Chem. Neurosci.2024, 15, 1378−1387.

9. Kaijin Zhang#, Junyu Liu#, Yuqi Jiang#, Simin Sun, Rongrong Wang, Jingxian Sun, Chuanteng Ma, Yinghan Chen, Wenxue Wang, Xuewen Hou, Tianjiao Zhu, Guojian Zhang, Qian Che, Robert A. Keyzers, Ming Liu and Dehai Li*. Sorbremnoids A and B: Promising NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways. J. Am. Chem. Soc. 2024, https://doi.org/10.1021/jacs.4c06538

10. Chunxiao Sun#, Yuqi Jiang#, Changlong Li#, Simin Sun, Jiaqi Lin, Wenxue Wang, Luning Zhou, Liping Li, Mudassir Shah, Qian Che, Guojian Zhang, De Wang, Tianjiao Zhu, Dehai Li*. Discovery, Total Synthesis, and Anti-inflammatory Evaluation of Naturally Occurring Naphthopyrone-Macrolide Hybrids as Potent NLRP3 Inflammasome Inhibitors. Angew. Chem. Int. Ed.2024, e202405860, https://doi.org/10.1002/anie.202405860

11. Jiajin Wu#, Wenxue Wang#, Yuhuan Yang, Mudassir Shah, Jixing Peng, Luning Zhou, Guojian Zhang, Qian Che, Jing Li, Tianjiao Zhu*, Dehai Li*. Phenylhydrazone Alkaloids from the Deep-Sea Cold Seep Derived Fungus Talaromyces amestolkiae HDN21-0307. J. Nat. Prod. 2024, 87, 5, 1407–1415.

12. Zuodong Wu, Wenxue Wang, Jilong Li, Chuanteng Ma, Liangzhen Chen, Qian Che, Guojian Zhang, Tianjiao Zhu, and Dehai Li*. Evolution-Based Discovery of Polyketide Acylated Valine from a Cytochalasin-Like Gene Cluster in Simplicillium lamelliciola HDN13430. J. Nat. Prod.2024, 87, 4, 1222–1229.

13. Xiaotian Yu#, Chuanteng Ma#, Wenxue Wang#, Jing Ge, Zian Wang, Jiaqi Lin, Qian Che, Guojian Zhang, Tianjiao Zhu, Dehai Li*. Genome Mining Reveals a UbiA-Type Prenyltransferase Access to Farnesylation of Diketopiperazines. Org. Lett. 2024, 26, 16, 3349–3354.

14. Chuanteng Ma#, Wenxue Wang#, Kaijin Zhang, Falei Zhang, Yimin Chang, Chunxiao Sun, Qian Che, Tianjiao Zhu, Guojian Zhang, Dehai Li*. Exploring the Diverse Landscape of Fungal Cytochrome P450-Catalyzed Regio- and Stereoselective Dimerization of Diketopiperazines. Adv. Sci.2024, 2310018-2310028.

15. Zhenhao Wang, Yuliang Tang, Ruyu Li, Shuai Tian, Yu Tang*, Dehai Li*. Bioinspired synthesis of cochlearol B and ganocin A Author links open overlay panel. Chin. Chem. Lett.2024, 35, 109247-109352.

16. Xinyu Liu, Fangfang Zhu, Manjaly J. Ajitha, Yunfeng Zhang, Kuo-Wei Huang*, Dehai Li*, De Wang*. Organocatalyzed Enantioselective [2 + 2] Cycloaddition of C,N-Cyclic Ketimines and Allenoates. Org. Lett. 2024, 26, 1, 225–230

17. Xuxiu Lu, Fengli Yuan, Liang Qiao, Yankai Liu, Qianqun Gu, Xin Qi, Jing Li, Dehai Li⁎, Ming Liu⁎. AS1041, a novel derivative of marine natural compound Aspergiolide A, induces senescence of leukemia cells via oxidative stress-induced DNA damage and BCR-ABL degradation. Biomed. Pharmacother.2024, 171, 116099-116110

18. Bohan Li, Lianghao Huang, Jiaqi Lin, Xiaoyao Ma, Yanan Luo, Wenrui Gai, Yingqi Xie, Tianjiao Zhu, Wei Wang*, Dehai Li*. Design, synthesis, and biological evaluation of novel penindolone derivatives as potential inhibitors of hemagglutinin-mediated membrane fusion. Eur. J. Med. Chem. 2023, 258, 115615-115623.

19. Lusheng Wang, Shikun Zong, Haotian Wang, Chengzhu Wu, Guangwei Wu, Feng Li, Guihong Yu, Dehai Li*, Meilin Zhu*. Dothideomins A−D, Antibacterial Polycyclic Bisanthraquinones from the Endophytic Fungus Dothideomycetes sp. BMC-101. J. Nat. Prod.2022, 85, 2789-2795

20. Yumeng Wu#, Xuanxuan Du#, Xianyang Wang, Hainan Liu, Luning Zhou, Yu Tang*, Dehai Li*. Bio-inspired construction of a tetracyclic ring system with an avarane skeleton: total synthesis of dactyloquinone A. Org. Chem. Front. 2022, 9 (17), 4705-4711.

21. Li Xing#, Yimin Chang*, Xiaoqian Zhang, Xuewen Hou, Yaxin Han, Mudassir Shah, Tianjiao Zhu, Jixing Peng, Guojian Zhang, Qian Che*, Dehai Li*. Dimeric Tetracenomycin Derivatives from a Taklamakan Desert-Derived Streptomyces sp. HDN154193. J. Nat. Prod.2022, 85, 301−305

22. Guihong Yu#, Peng Sun#, Reyilamu Aierken, Chunxiao Sun, Zhenzhen Zhang, Qian Che, Guojian Zhang, Tianjiao Zhu, Qianqun Gu, Mingyu Li*, Dehai Li*. Linear polyketides produced by co-culture of Penicillium crustosum and Penicillium fellutanum. Mar. Life Sci. Tech. 20224, 237–244

23. Guoliang Zhou, Tianjiao Zhu, Qian Che, Guojian Zhang*, Dehai Li*. Structural diversity and biological activity of natural p‑terphenyls. Mar. Life Sci. Tech. 2022,4, 62–73

24. Guangwei Wu*, Xuan Qian, Yeqiang Huang, Yujia Liu, Luning Zhou, Wei Wang, Jing Li, Tianjiao Zhu, Qianqun Gu, and Dehai Li*. Nonenzymatic Self-Assembly Access to Diverse ortho-Quinone Methide-Based Pseudonatural Products. Org. Lett.2022, 24, 5235–5239

25. Zhixin Liu, Xinyu Liu, Shengkuan Yang, Xiaohe Miao, Dehai Li*, and De Wang*. Titanium-Mediated aza-Nazarov Annulation for the Synthesis of N-Fused Tricycles: A General Method to Access Lamellarin Analogues. J. Org. Chem.2022, 87, 15, 10319–10332

26. Chunxiao Sun#, Qianwen Liu#, Mudassir Shah, Qian Che, Guojian Zhang, Tianjiao Zhu, Jianfeng Zhou, Xiaozhi Rong*, Dehai Li*. Talaverrucin A, Heterodimeric Oxaphenalenone from Antarctica Sponge-Derived Fungus Talaromyces sp. HDN151403, Inhibits Wnt/β-Catenin Signaling Pathway. Org. Lett.2022, 24, 3993–3997

27. Chunxiao Sun#, Xiaoyu Liu#, Ning Sun, Xiaomin Zhang, Mudassir Shah, Guojian Zhang, Qian Che, Tianjiao Zhu, Jing Li*, Dehai Li*. Cytotoxic Nitrobenzoyl Sesquiterpenoids from an Antarctica Sponge-Derived Aspergillus insulicola. J. Nat. Prod.2022,85, 4, 987–996

28. Kaijin Zhang#, Guojian Zhang#, Xuewen Hou, Chuanteng Ma, Junyu Liu, Qian Che, Tianjiao Zhu, Dehai Li*. A Fungal Promiscuous UbiA Prenyltransferase Expands the Struc-tural Diversity of Chrodrimanin-Type Meroterpenoids.Org. Lett.2022, 24, 2025−2029

29. Yi Zhao#, Chunxiao Sun#, Luyao Huang, Xiao Zhang, Guojian Zhang, Qian Che, Dehai Li*, Tianjiao Zhu*. Talarodrides A–F, Nonadrides from the Antarctic Sponge-Derived Fungus Talaromyces sp. HDN1820200. J. Nat. Prod.2021, 84, 12, 3011–3019

30. Luning Zhou, Xuedong Chen, Chunxiao Sun, Yimin Chang, Xiaofei Huang, Tianjiao Zhu, Guojian Zhang, Qian Che*, Dehai Li*. Saliniquinone Derivatives, Saliniquinones G−I and Heraclemycin E, from the Marine Animal-derived Nocardiopsis aegyptia HDN19-252. Mar. Drugs, 2021, 19, 575-584.

31. Yimin Chang#, Qian Che#, Li Xing, Chuanteng Ma, Yaxin Han, Tianjiao Zhu, Blaine A. Pfeifer, Jixing Peng, Guojian Zhang*, and Dehai Li*. Antibacterial p-Terphenyl with a Rare 2,2′-Bithiazole Substructure and Related Compounds Isolated from the Marine-Derived Actinomycete Nocardiopsis sp. HDN154086. J. Nat. Prod.2021, 84, 4, 1226–1231

32. Lu Wang#, Yeqin Shi#, Qian Che, Tianjiao Zhu, Guojian Zhang, Xiaokun Zhang, Mingyu Li*, Dehai Li*. Penipyrols C−G and methyl-penipyrol A, α-Pyrone Polyketides from the Mangrove Derived Fungus Penicillium sp. HDN-11-131.Bioorg. Chem.2021,113, 104975-104980

33. Guoliang Zhou, Chunxiao Sun, Xuewen Hou, Qian Che, Guojian Zhang, Qianqun Gu, Chenguang Liu, Tianjiao Zhu*, Dehai Li*. Ascandinines A-D, Indole Diterpenoids from the Sponge-derived Fungus Aspergillus candidus HDN15-152. J. Org. Chem. 2021, 86(3):2431-2436

34. Feng Li, Chunxiao Sun, Qian Che, Tianjiao Zhu, Qianqun Gu, Huashi Guan, Guojian Zhang, Dehai Li*. Pyrazinopyrimidine alkaloids from a mangrove-derived fungus Aspergillus versicolor HDN11-84. Phytochemistry 2021, 188, 112817-112823

35. Liping Li#, Zhongwei Duan#, Donghui Bai#, Fang Lu, Jiejie Hao, Tianjiao Zhu*, Deihai Li*. Design, synthesis and lipid-lowering activities of penipyridone derivatives.Bioorg. Med. Chem.2021, 40, 116192-116203

36. Yuying Wang#, Lulu Sun#, Guihong Yu, Xin Qi, Aotong Zhang, Zhimin Lu, Dehai Li*, Jing Li*. Identification of a novel non-ATP-competitive protein kinase inhibitor of PGK1 from marine nature products.Biochem. Pharmacol.2021, 183, 114343-114353

37. Jiajia Dai#，Meilin Zhu#， Xin Qi， Yanjuan Wang， Huilin Li， Shuai Tang， Qiang Wang， Ao Chen， Ming Liu，Qianqun Gu， Dehai Li*， Jing Li*. Fungal mycotoxin penisuloxazin A, a novel C-terminal Hsp90 inhibitor and characteristics of its analogues on Hsp90 function related to binding sites,Biochem. Pharmacol.2020, 182, 114218-114232.

38. Chunxiao Sun, Shah Mudassir, Zhenzhen Zhang, Yanyan Feng, Yimin Chang, Qian Che, Qianqun Gu, Tianjiao Zhu, Guojian Zhang*, Dehai Li*. Secondary Metabolites from Deep-sea Derived Microorganisms. Curr. Med. Chem.2020, 27(36): 6244-6273

39. Qi Gan#, Chunyu Lin#, Changjun Lu, Yimin Chang, Qian Che, Guojian Zhang, Tianjiao Zhu, Qianqun Gu, Zhiqiang Wu, Mingyu Li*, Dehai Li*. Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus. J. Nat. Prod. 2020, 83,10, 2996-3003.

40. Junxiao Wang#, Haotian Wang#, Chunxiao Sun, Fenge Li, Yingqiang Wu, Guojian Zhang, Qianqun Gu, Tianjiao Zhu, Dehai Li, and Qian Che*. Dimeric Tetrahydroanthracene Regioisomers and Their Monomeric Precursor Produced by Streptomyces fumigatiscleroticus HDN10255.J. Nat. Prod. 2020, 83, 9, 2797–2802

41. Yimin Chang, Li Xing, Chunxiao Sun, Shuang Liang, Tao Liu, Xiaomin Zhang, Tianjiao Zhu, Blaine A. Pfeifer, Qian Che, Guojian Zhang, Dehai Li*. Monacycliones G−K and Ent-gephyromycin A, Angucycline Derivatives from the Marine-Derived Streptomyces sp. HDN15129. J. Nat. Prod.2020,83, 9, 2749–2755.

42. Meilin Zhu, Zhen Yang, Haotian Wang, Qi Gan, Guojian Zhang, Qian Che, Tianjiao Zhu, Qianqun Gu, Bingnan Han,* and Dehai Li*. Penispirozines A–H, Three Classes of Dioxopiperazine Alkaloids with Spirocyclic Skeletons Isolated from the Mangrove-Derived Penicillium janthinellum. J. Nat. Prod.2020,83, 9, 2647–2654.

43. Wenxue Wang, Huimin Feng, Chunxiao Sun, Qian Che, Guojian Zhang, Tianjiao Zhu, Dehai Li∗. Thiocladospolides F-J, antibacterial sulfur containing 12-membered macrolides from the mangrove endophytic fungus Cladosporium oxysporum HDN13-314. Phytochemistry, 2020, 178, 112462-112469

44. Guangwei Wu#, Guihong Yu#, Yunjia Yu#, Shuang Yang#, Zhongwei Duan, Wei Wang*, Yankai Liu, Rilei Yu, Jing Li, Tianjiao Zhu, Qianqun Gu, Dehai Li*. Chemoreactive-inspired discovery of influenza A virus dual inhibitor to block hemagglutinin-mediated adsorption and membrane fusion. J. Med. Chem.2020,63, 13, 6924–6940

45. Meilin Zhu, Xuewen Zhang, Xuenan Huang, Haotian Wang, Komal Anjum, Qianqun Gu, Tianjiao Zhu, Guojian Zhang, Dehai Li*. Irregularly Bridged Epipolythiodioxopiperazines and Related Analogues: Sources, Structures and Biological Activities. J. Nat. Prod. 2020, 83, 6, 2045–2053

46. Qiuying Wang, Kaijin Zhang, Wei Wang, Guojian Zhang, Tianjiao Zhu, Qian Che, Qianqun Gu, Dehai Li*. Amphiepicoccins A−J: Epipolythiodioxopiperazines from the Fish-Gill-Derived Fungus Epicoccum nigrum HDN17-88.J. Nat. Prod.2020, 83, 2, 524–531

47. Guoliang Zhou, Xiaohui Chen, Xiaomin Zhang, Qian Che, Guojian Zhang, Tianjiao Zhu, Qianqun Gu, Dehai Li*. Prenylated p-Terphenyls from a Mangrove Endophytic Fungus, Aspergillus candidus LDJ5. J. Nat. Prod.2020, 83, 1, 8–13