张国建

张国建

博士

教授

博士生导师

科 室：

微生物与生化药学

电子邮箱：

zhangguojian@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海洋馆205 266003

研究方向：

1.         药用微生物资源发掘和天然药物分子的发现

2.         活性分子的生物合成和微生物代谢工程

个人简介

张国建，医学博士、教授、硕士/博士生导师，山东省泰山学者青年专家，中国海洋大学“青年英才工程”第一层次教授。主要从事活性天然产物分子的发现、生物合成及微生物代谢工程研究。近年来获得了300余个活性新结构，阐明多个活性天然产物的生物合成过程，并基于原核和真核细胞异源表达体系实现了大环内酯糖苷、角环素、以及硫代二酮哌嗪等多个活性药源分子的高效生产。在Sci. Adv., Metab. Eng., Curr. Opin. Biotech., J. Nat. Prod.等期刊发表SCI收录论文40余篇发表高水平学术论文40余篇；申请国家发明专利6项，获授权3项；主持国家自然科学基金面上（41976105，32370061），参与国家自然科学基金重大项目（81991522）、国家重点研发项目（2019YFC0312500）等课题。担任Curr. Opin. Biotech., Fermentation等杂志客座编辑和中国抗生素杂志青年编委，中国药理学会海洋药理专业委员会青年委员，并担任ACS Synth. Biol., J. Nat. Prod., App. Microbial. Biotechnol.等二十余个期刊审稿工作。

教育背景

2006-2011

中国海洋大学

药物化学

博士

2002-2006

中国海洋大学

生物技术

学士

工作经历

2017-至今

中国海洋大学医药学院

副教授、教授

2014-2016

俄克拉荷马大学

博士后

2012-2014

纽约州立大学

博士后

学术兼职

Curr. Opin. Biotech., Fermentation等杂志客座编辑、中国抗生素杂志青年编委；中国药理学会海洋药理专业委员会青年委员；担任ACS Synth. Biol., J. Nat. Prod., App. Microbial. Biotechnol.等三十余个期刊审稿工作。

荣誉奖励

2020泰山学者青年专家

承担课程

药学分子生物学（本科生课程）

基因工程技术 （本科生国际课程）

海洋微生物药物（研究生课程）

药学前沿 （博士生课程）

Marine Natural Products（研究生国际课程）

研究进展

1、基于基因组分析采掘，结合现代天然产物化学研究方法开发海洋微生物代谢潜能，获得了联苯杂环类、特拉姆酸类、混源萜以及寡肽类等多种结构新颖的天然产物。上述结构在抗肿瘤、抗炎、抗感染等领域表现出了良好的应用潜力。

2、利用代谢工程、组合生物合成和异源表达技术改造和优化天然产物生物合成途径，获得工程化菌株和结构新颖的天然产物分子。前期利用大肠杆菌宿主成功完成了红霉素、水杨酸糖苷衍生物、麦角硫因等系列药物功能分子的异源表达。目前开展针对于莽草酸途径的代谢工程研究以及萜类（混源杂萜）、多肽（抗菌肽）和二酮哌嗪（多硫代二酮哌嗪）等活性分子的生物合成研究。

代表性成果

代表性论文

1.         Xiaolin Liu, Kang Li, Jing Yu, Chuanteng Ma, Qian Che, Tianjiao Zhu, Dehai Li, Blaine A. Pfeifer*, and Guojian Zhang*. Cyclo-diphenylalanine Production in Aspergillus nidulans through Stepwise Metabolic Engineering. Metab. Eng. 2024, 82, 147-156.

2.         Yimin Chang, Luning Zhou, Xuewen Hou, Tianjiao Zhu, Blaine A. Pfeifer, Dehai Li, Xiaoxi He,* Guojian Zhang,* and Qian Che*. Microbial Dimerization and Chlorination of Isoflavones by a Takla Makan Desert-Derived Streptomyces sp. HDN154127. J. Nat. Prod. 2023, 86, 1, 34–44.

3.         Guowei Liu, Dan Liu, Zongyuan Li, Jieying Jiao, Xuewen Hou, Xiaomin Zhang, Qian Che, Tianjiao Zhu, Dehai Li, Guojian Zhang*. Overexpression of transcriptional regulator and tailoring enzyme leads to the discovery of anti-inflammatory meroterpenoids from marinederived fungus Alternaria alternata JJY-32. Fron. Mar. Sci., 2022, DOI: 10.3389/fmars.2022.1015684.

4.         Xuewen Hou, Changlong Li, Runfang Zhang, Yinping Li, Huadong Li, Yundong Zhang, Han-Shen Tae, Rilei Yu, Qian Che, Tianjiao Zhu, Dehai Li*, Guojian Zhang*. Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived PsychrophilicPseudogymnoascus sp. HDN17-933. Mar. Drugs, 2022, 20, 593.

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

6.         Xuewen Hou, Ruonan Sun, Yanyan Feng, Runfang Zhang, Tianjiao Zhu, Qian Che, Guojian Zhang*, Dehai Li*. Peptaibols: diversity, bioactivity, and biosynthesis. Eng. Microbiol., 2022, 2, 100026.

7.         Zilu Tang, Yimin Chang, Tianjiao Zhu, Qian Che, Dehai Li*, Guojian Zhang*. Antibacterial angucyclinone and α-pyrone derivatives from desert-derived Nocardiopsis dassonvillei HDN 154151. J. Antibiot., 2022, 75, 380-384.

8.         Guoliang Zhou, Tianjiao Zhu, Qian Che, Guojian Zhang*, Dehai Li*. Structural diversity and biological activity of natural p-terphenyls. MLST., 2022, 4, 62-73.

9.         Yimin Chang, Qian Che, Li Xing, Chuanteng Ma, Yaxin Han, Tianjiao Zhu, Blaine A. Pfeifer, Jixing Peng, Guojian Zhang* and Dehai Li*. Antibacterial p-Terphenyls with rare 2,2'-bithiazole moiety isolated from marine-derived actinomycete Nocardiopsis sp. HDN154086. J. Nat. Prod. 2021, 84, 4, 1226–1231.

10.     Guoliang Zhou, Tianjiao Zhu, Qian Che, Guojian Zhang*, Dehai Li*. Structural diversity and biological activity of natural p-terphenyls. MLST., 2021, DOI:10.1007/s42995-021-00117-8.

11.     Chuanteng Ma, Kaijin Zhang, Xianyan Zhang, Guowei Liu, Tianjiao Zhu, Qian Che, Dehai Li and Guojian Zhang*. Heterologous expression and metabolic engineering tools for improving terpenoids production. Curr. Opin. Biotech., 2021, 69, 281-289.

12.     Ruonan Sun, Yanyan Feng, Hengyi Xu, Xuewen Hou, Tianjiao Zhu, Qian Che, Blaine Pfeifer, Guojian Zhang* and Dehai Li*. An Efficient Marker Recycling System for Sequential Gene Deletion in a Deep Sea-derived Fungus Acremonium sp. HDN16-126. Synth. Syst. Biotechnol., 2021, 6, 2, 127-133.

13.     Lu Wang, Xianyan Zhang, Kaijin Zhang, Xiaomin Zhang, Tianjiao Zhu, Qian Che, Guojian Zhang* and Dehai Li*. Overexpression of Global Regulator brlaeA Leads to the Discovery of New Polyketide in Fungus Penicillium rocae HDN-12-143. Front. Chem., 2020, online. DIO: 89/fchem.2020.00270.

14.     Lu Wang, Jieying Jiao, Dan Liu, Xiaomin Zhang, Jing Li, Qian Che, Tianjiao Zhu, Dehai Li* and Guojian Zhang*. Cytotoxic Meroterpenoids from the Sponge‐Associated Fungus Alternaria sp. JJY‐32. Chem. Biodivers., 2020, 17, e2000226. Front.

15.     Xueping Ge, Chunxiao Sun, Yanyan Feng, Lingzhi Wang, Jixing Peng, Qian Che, Qianquan Gu, Tianjiao Zhu, Dehai Li and Guojian Zhang*. Anthraquinone Derivatives from a Marine-Derived Fungus Sporendonema casei HDN16-802. Mar. Drugs, 2019, 17:334.

16.     Tingting Zhao, Yimin Chang, Tianjiao Zhu, Jing Li, Qianqun Gu, Dehai Li, Qian Che* and Guojian Zhang*. α-Pyrone derivatives with cyto-protective activity from two Takla Makan Desert Soil Derived Actinomycete Nocardiopsis Strains Recovered in Seawater Based Medium. Nat. Prod. Res., 2019, 33(17), 2498-2506.

17.     Chunxiao Sun, Shah Mudassir, Zhenzhen Zhang, Yanyan Feng, Yimin Chang, Qian Che, Qianqun Gu, Tianjiao Zhu, Guojian Zhang* and Dehai Li*. Secondary Metabolites from Deep-Sea Derived Microorganism. Curr. Med. Chem. 2019, DIO: 10.2174/0929867326666190618153950.

18.     Guihong Yu, Guangwei Wu, Zichao Sun, Xiaomin Zhang, Qian Che, Qianqun Gu, Tianjiao Zhu, Dehai Li and Guojian Zhang*. Cytotoxic tetrahydroxanthone dimers from the mangrove-associated fungus Aspergillus versicolor HDN1009, Mar. Drugs, 2018, 16:335.

19.     Lei Fang#, Guojian Zhang#*, Omar El-Halfawy, Eric D. Brown and Blaine. A. Pfeifer*. Broadened Glycosylation Patterning of Heterologously Produced Erythromycin. Biotechnol. Bioeng., 2018, 115, 2771-2777.

20.     Zhenzhen Zhang, Xueqian He, Guangwei Wu, Congcong Liu, Changjun Lu, Qianqun Gu, Qian Che, Tianjiao Zhu, Guojian Zhang,* and Dehai Li*. Aniline-tetramic Acids from the Deep-sea Derived Fungus Cladosporium sphaerospermum L3P3 Cultured with the HDAC Inhibitor SAHA. J. Nat. Prod. 2018, 81 (7), 1651–1657.

21.     Ruiquan Qi, Blaine A Pfeifer* and Guojian Zhang*, Engineering heterologous production of salicylate glucoside and glycosylated variants. Front. Microbiol., 2018, 9, 2441.

22.     Zhenzhen Zhang, Xueqian He, Qian Che, Guojian Zhang*, Tianjiao Zhu, Qianqun Gu and Dehai Li*. Sorbicillasins A-B and Scirpyrone K from a Deep-Sea-Derived Fungus, Phialocephala sp. FL30r. Mar. Drugs, 2018, 16 :245.

23.     Charles H Jones#, Guojian Zhang#, Roozbeh Nayerhoda, Marie Beitelshees, Andrew Hill, Pooya Rostami, Yi Li, Bruce A Davidson, Paul Knight, Blaine A Pfeifer. Comprehensive vaccine design for commensal disease progression. Sci. Adv., 2017, 3, e1701797. (#Co-first author).

24.     Guojian Zhang, Jing Li, Tianjiao Zhu, Qianqun Gu and Dehai Li. Advanced tools in marine natural drug discovery. Curr. Opin. Biotech. 2016, 43, 13-23.

25.     Guojian Zhang, Yi Li, Lei Fang and Blaine A. Pfeifer. Tailoring Pathway Modularity in the Biosynthesis of Erythromycin Analogues Heterologously Engineered in E. coli. Sci. Adv., 2015, 1, e1500077.

26.     Guojian Zhang, Guangwei Wu, Tianjiao Zhu, Tibor Kurtán, Attila Mándi, Jieying Jiao, Jing Li, Xin Qi, Qianqun Gu, and Dehai Li. Meroterpenoids with Diverse Ring Systems from the Sponge-Associated Fungus Alternaria sp. JJY-32. J. Nat. Prod., 2013, 76, 1946–1957.

27.     Xinying Yang#, Guojian Zhang#, Xuelian Tang, Jieying Jiao, Sung Yeon Kim, Joo Young Lee, Tianjiao Zhu, Dehai Li, Yong Gab Yun and Qianqun Gu. Toll-like Receptor 4/Nuclear Factor-κB Signaling Pathway is Involved in ACTG-toxin H-mediated Anti-inflammatory Effect. Mol. Cell. Biochem., 2013, 374, 29-36. (#Co-first author).

28.     Guojian Zhang, Shiwei Sun, Tianjiao Zhu, Zhenjian Lin, Jingyan Gu, Dehai Li and Qian-qun Gu. Antiviral Isoindolone Derivatives from an Endophytic Fungus Emericella sp. Associated with Aegiceras corniculatum.Phytochemistry, 2011, 72, 1436-1442.

参编英文专著

1.         Ruiquan Qi, Guojian Zhang, B.A. Pfeifer. In Engineering Escherichia coli for bacterial natural product production. Chaitan Khosla, Sean Brady, Jay Keasling, Eds; Comprehensive Natural Products III: Chemistry and Biology. Elsevier, 2019.

2.         Lei Fang, Guojian Zhang, Blaine A Pfeifer. In Engineering of E. coli for Heterologous Expression of Secondary Metabolite Biosynthesis Pathways Recovered from Metagenomics Libraries; Trevor C. Charles, Mark R. Liles, Angela Sessitsch, Eds; Functional Metagenomics: Tools and Applications. Springer-Verlag London Ltd, 2017.

3.         Guojian Zhang and Blaine A. Pfeifer. In Production of Therapeutic Products; Anne Osbourn, Rebecca Goss, Guy T. Carter, Eds; Natural Products: Discourse, Diversity, and Design; Wiley-Blackwell Ltd, 2014.

4.         Yi Li, Guojian Zhang, Blaine A. Pfeifer. In Current and Emerging Options for Taxol Production; Jens Schrader, Jörg Bohlmann, Eds; Biotechnology of Isoprenoids. Springer-Verlag London Ltd, 2014.

专利

1.         一种抗肿瘤聚酮类化合物及其制备方法和用途，发明人：张国建，徐晓，朱天骄，李德海，顾谦群，车茜，国家发明专利，202111428174.4

2.         生产环（L-苯丙氨酸-L-苯丙氨酸）的工程菌及其构建方法和应用，发明人：张国建、刘小林、李德海、朱天骄、车茜，国家发明专利，202310298081.7

3.         一种吲哚生物碱类衍生物的制备方法和用途，发明人：李德海，李博涵，王伟，朱天骄，车茜，张洋，张国建，国家发明专利，2023115448611

4.         倍半萜混对二酚类化合物及其制备方法和用途，发明人：李德海，顾谦群，张国建，朱天骄，国家发明专利，201010119062.6

项目课题

1.         2020.01-2023.12 国家自然科学基金面上项目（41976105），主持，74.4万元

2.         2024.01-2027.12 国家自然科学基金面上项目（32370061），主持，62.0万元

3.         2021.01-2025.12 山东省泰山学者青年专家项目（tsqn202103153），主持 50.0万元

4.         2020.01-2024.12国家自然科学基金重大项目（81991522），参与，50.0万元

5.         2019.08-2021.12 国家重点研发项目（2019YFC0312500），参与，主持子任务，110.0万元

6.         2017.07-2022.07中国海洋大学青年英才工程项目启动基金，主持，15.0万元

7.         2019.06-2021.06  海洋科学与技术国家试点实验室开放基金，参与，7.5万元