汤亚杰(yajietang@sdu.edu.cn)

304浏览器永利集团特聘教授、博士生/硕士生导师、国家杰出青年科学基金获得者

2003-2005美国麻省理工学院(MIT)博士后

2009 “新世纪百千万人才工程”国家级人选

2012 Spring学术期刊“Bioprocess and Biosystems Engineering”副主编

2014 全国杰出专业技术人才

2014 国家“万人计划”科技创新领军人才

2016 国家杰出青年科学基金

2017 中国化工学会候德榜化工科技创新奖

2024 英国皇家生物学会会士

2024 英国皇家化学学会会士

研究方向：天然药物生物智造

长期致力于“天然药物生物智造”领域的教学与科研，建立了天然产物“新分子、新反应、新药物”上下贯通的“天然药物生物智造”研究新范式，为天然产物“出新率低、成药性差、合成效率低”研究瓶颈的突破提供解决方案。

1.新分子：以鬼臼毒素作为研究对象，基于百万级药靶、千万级活性毒性药代、亿级小分子化合物等数据库，构建预测分子结构改造的多任务学习训练集。基于临床患者需求建立人工智能辅助药物分子设计系统，采用trRosetta、diffusion等算法，全方位迭代学习成药性，自主搭建药物分子智能设计模型。设计靶向性强、高效低毒、生物利用度高的鬼臼类衍生物。

2.新反应：基于化学结构与反应规则相似性的RetroPath2.0等软件及分子设计的逆diffusion结构片段组装过程，构建目标产物生物合成途径的智能设计系统。探究非天然供体引入及其手性控制的酶学机理，建立目标产物人工生物合成途径，实现目标产物的“从无到有”。阐明人工生物合成途径与底盘细胞的适配机制，构建合成效率提升的细胞工厂，实现目标产物的“从低到高”。

3.新药物：以临床价值为导向的新药创制为目标，构建临床肿瘤组织来源的不同分型癌症PDO和PDX药效评价模型，从新分子库中挖掘高活低毒的鬼臼类候选药物。深入开展候选药物的药代/毒代等成药性研究，推进候选药物申报临床试验，努力开发为具有全新抗肿瘤机制I类抗肿瘤新药。

主持科研项目

2017.1-2021.12天然产物生物制造国家杰出青年科学基金(21625602)

2019.1-2023.12含氮杂环鬼臼类候选药物人工合成途径的体内组装国家自然科学基金重点项目(21838002)

2020.1-2024.12新天然与人工产物的定向挖掘和高效合成的平台技术 国家重点研发计划“合成生物学”重点专项(2019YFA0905700)

2022.7-2027.6天然产物生物智造 山东省泰山学者攀登专家(tspd20221101)

科研获奖

2016 湖北省自然科学一等奖天然产物生物制造的理论与方法

2014 湖北省科技进步一等奖 工业微生物发酵关键技术及产业化

2014 教育部自然科学一等奖 高等真菌和植物的次级代谢物发酵过程调控

2011 湖北省自然科学二等奖食用菌液体发酵

2010 上海市自然科学二等奖生化反应工程调控方法研究

2004 教育部自然科学一等奖生物反应器细胞培养工程研究

国际发明专利

Ya-Jie Tang, Wei Zhao. 4-Sulfur substituted podophyllotoxin derivatives and preparation method thereof and use thereof (US 11,242,354 B2)

Ya-Jie Tang, Wei Zhao. 4β-anilino substituted podophyllotoxin derivatives preparation method thereof and use thereof (US 11,319,328 B2)

Ya-Jie Tang, Kai-Zhi Jia, Yang-Hua Xu, Quan Zhang, Hong-Mei Li. Methionine lyase encoding gene and biosynthetic method thereof (US 10,308,925 B2)

Ya-Jie Tang, Jian-Long Li, Wei Zhao, Hong-Mei Li. Sulfur-substituted podophyllotoxin derivative, synthesis method thereof, and use thereof (US 9,828,386 B2)

Ya-Jie Tang, Yong Yang, Wei Zhao, Hong-Mei Li. Anilino podophyllin derivative having antitumor activity, method for preparation thereof, and use thereof (US 9,714,254 B2)

Ya-Jie Tang, Wei Zhao. 4′-Demthylepipodophyllotoxin derivative, preparation method and use thereof II (US 8,796,279 B2)

Ya-Jie Tang. 4′-Demthylepipodophyllotoxinderivative, preparation method and use thereof (US 8,569,309 B2)

Ya-Jie Tang, Wei Zhao. Sulfur-substituted heterocycles podophyllotoxin derivatives having antitumor activity, method for preparation thereof, and use thereof (EP3686203)

Ya-Jie Tang, Wei Zhao. 4-硫黄置換ポドフィロトキシン系誘導体、その製造方法及び使用(特许第7052018号)

Ya-Jie Tang, Wei Zhao. Podophyllotoxinderivative, preparation method and use thereof (PCT/CN2023/10270286.4)

学术论文

1.Shan Wang^1,*, Kewen Wu¹,Ya-Jie Tang*,Hai Deng*. Dehydroamino acid residues in bioactive natural products.Natural Product Reports2024, 41: 273-297.(¹with equal contribution to this work)

2.Wei Zhao, Xiao-Di Zheng, Paula Yun-Zhi Tang, Hong-Mei Li, Xue Liu, Jian-Jiang Zhong,Ya-Jie Tang*. Advances of antitumor drug discovery in traditional Chinese medicine and natural active products by using multi-active components combination.Medicinal Research Reviews2023, 1:1-31.

3.Ying Cong, Shu-Yue Zhang,Paula Yunzhi Tang, Hong-Mei Li, Xue Liu, Wei Zhao*,Ya-Jie Tang*. Conjugating 4β-NH-(5-aminoindazole)-podophyllotoxin and galectin-1-targeted aptamer for synergistic chemo-immunotherapy of hepatocellular carcinoma.Advanced Healthcare Materials2023, 2203144:1-11.

4.Ying Cong, Shu-Yue Zhang,Hong-Mei Li,TaoChen,Jian-Jiang Zhong,Wei Zhao*,Ya-Jie Tang*. A truncated DNA aptamer with high selectivity for estrogen receptor-positive breast cancer cells.International Journal of Biological Macromolecules2023, 252:126450.

5.Wei Zhao¹, Cong Ying¹, Hong-Mei Li, Shengying Li, Yuemao Shen, Qingsheng Qi, Youming Zhang, Yue-zhong Li,Ya-Jie Tang*.Challenges and potential on improving druggability of podophyllotoxin-derived drugs in cancer chemotherapy.Natural Product Reports2021, 38: 470-488. (¹with equal contribution to this work)

6.Kai-Zhi Jia,Li-Wen Zhu,Xu-Dong Qu, Youming Zhang, Yue-zhong Li, Shengying Li, Yuemao Shen, Qingsheng Qi,Ya-Jie Tang*.EnzymaticO-glycosylation of etoposide aglycone by exploration of the substrate promiscuity for glycosyltransferases.ACSSynthetic Biology2019, 8:2718-2725.

7.Wei Zhao¹, Long He¹, Tian-Le Xiang, andYa-Jie Tang*.Discover 4β-NH-(6-aminoindole)-4-desoxy-podophyllotoxin with nanomolar-potency antitumor activity by improving the tubulin binding affinity on the basis of a potential binding site nearby colchicine domain.European Journal of Medicinal Chemistry2019, 170:73-86. (¹with equal contribution to this work)

8.Qing-Yun Zhang¹, Wei Zhao¹,Ya-Jie Tang*.Discover the leading compound of 4β-S-(5-fluorobenzoxazole)-4-deoxy-4'-demethylepipodophyllotoxin with millimolar-potency toxicity by modifying the molecule structure of podophyllotoxin.European Journal of Medicinal Chemistry2018, 158:951-964.(¹with equal contribution to this work)

9.Wei Zhao¹,ChenZhou¹, Ze-Yuan Guan, Fu-Sheng Chen*, Ping Yin*,Ya-Jie Tang*.Structural insights into the inhibition of tubulin by the antitumor agent 4β-S-(1, 2, 4-triazole-3-yl)-podophyllotoxin.ACS Chemical Biology2017,12:746-752 (¹with equal contribution to this work)

10.Ya-Jie Tang*, Wei Zhao, Hong-Mei Li. Novel tandem biotransformation process for the biosynthesis of a novel compound 4-(2, 3, 5, 6-tetramethylpyrazine-1)-4′-demethylepipodophyllotoxin.Applied and Environmental Microbiology2011,77:3023-3034.

招贤纳士

长期高薪诚聘具有生物学(合成微生物学、结构生物学)、化学(化学生物学、天然产物全合成)、药学等相关研究背景的各类青年才俊(本科生、硕士生、科研助理、科研秘书、博士后、专聘科技人员、预聘制科研教师、齐鲁青年学者、泰山学者、国家四青等)。有意申请者请将详细的个人简历(包含但不限于学习和工作经历、研究工作总结、学术成果及佐证材料等)发送邮件至yajietang@sdu.edu.cn。邮件主题请写“申请者姓名+应聘的职位”，经面试考核后择优录取。