合成生物学平台

undefined

瞿旭东

  • 教育背景

  • 工作经历

  • 研究方向

  • 荣誉奖励/承担项目

  • 代表性论文专著

  • 2002.09-2007.07:中国科学院上海有机化学研究所,博士

  • 1998.09-2002.07:华东师范大学化学系,本科

  • 2022.10-至今:上海交通大学张江高等研究员,教授(兼)

  • 2020.09-至今:上海交通大学生命科学技术学院,教授

  • 2012.01-2020.08:武汉大学药学院,教授

  • 2011.01-2011.12:中国科学院上海有机化学研究所,副研究员

  • 2008.11-2010.12:中国科学院上海有机化学研究所,助理研究员

  • 2007.09-2008.10:美国麻省理工学院化学系,博士后

  • 天然产物是新药研发的重要来源,但其成药性高度依赖结构优化。由于复杂天然产物骨架中富含化学惰性碳原子,实现碳骨架的选择性化学修饰极具挑战,长期被视为天然药物研发的难点;在制备方面,多数动植物来源的天然药物仍依赖提取或全合成,效率低、成本高。合成生物技术虽提供了新途径,但受限于关键酶元件的稀缺与专一性,其应用范围与效率仍十分局限。因此,发展高效、普适的碳骨架修饰与合成方法,已成为当前药物研发与生产领域的关键瓶颈与前沿方向。

    本实验室长期致力于天然产物生物合成研究,遵循“机制解析—过程控制—高效创制”的研究路径。一方面,通过解析碳链合酶在催化、组装与环合中的核心机制,结合酶工程与合成生物学手段,精准调控碳链构建过程,实现重要天然产物的定向合成与活性创新(Bottom-Up策略)。另一方面,采用Top-Down策略,阐明碳链降解酶系的催化机制,借助酶设计与工程化改造,精准调控碳链拆解过程,从而以廉价原料高效合成关键药物。

    我们致力于融合生物合成与化学合成策略,构建针对重要天然产物的定向生物合成理论与技术体系,实现对碳骨架的普适、高效、精准的合成与编辑,以拓展结构多样性、提升药物生产效率,推动天然药物资源的深度开发与高效创制。

荣誉奖励:

  • 2024 国家级高层次人才

  • 2023 国家技术标准创新基地(乳业)金鬲创新奖

  • 2023 中央高校优秀青年团队带头人

  • 2022 上海市优秀学术带头人

  • 2013 国家优秀青年科学基金

  • 2012 国家级优秀青年人才

  • 2012 武汉大学珞珈学者

承担项目

  • 2025-2028:国家重点研发计划/合成生物学重点专项/项目

  • 2025-2029:国家重点研发计划/合成生物学重点专项/任务

  • 2025-2029:国家杰出青年科学基金

  • 2023-2025:企业开发项目/甾体生物转化技术

  • 2023-2025:中央高校优秀青年团队培育项目

  • 2023-2026:上海市自然科学基金/面上项目

  • 2023-2026:国家自然科学基金/面上项目

  • 2022-2025:上海市优秀学术带头人

  • 2020-2023:国家自然科学基金/面上项目

  • 2020-2023:企业开发项目/甾体生物转化技术

  • 2019-2024:国家重点研发计划/高版本工业放线菌底盘/任务

  • 2018-2021:国家重点研发计划/中药资源合成生物学研究/课题

  • 2018-2021:国家自然科学基金/面上项目

  • 2016-2019:国家自然科学基金/面上项目

  • 2014-2016:国家优秀青年科学基金

  • 2013-2016:国家自然科学基金/面上项目

  • 2013-2015:教育部新世纪优秀人才支持计划

  • 2010-2012:国家自然科学基金/青年项目

  • Yeqing Du, Guangzheng Wei, Tai-Ping Zhou, Yuhan Dai, Wenya Tian, Mancheng Tang, Zixin Deng, Binju Wang, Xudong Qu. P450-mediated dual cyclization mechanisms for pyrroloindoline unit formation in bispyrrolidinoindoline diketopiperazine alkaloid biosynthesis. J. Am. Chem. Soc. 2025, in press.

  • Wenya Tian, Guangzheng Wei, Borui Duan, Haidong Peng, Huanhuan Liu, Mengmeng Zheng, Zhi Lin, Zixin Deng, Zhengyu Zhang, Xudong Qu. Unveiling bacterial cytochrome P450 enzymes that catalyze steroid side-chain cleavage. Nat. Commun. 2025, in press.

  • Kai Jiang, Yan Gao, Yuhan Dai, Xiaoli Yan, Lu Yang, Ming Jiang, Zhi Lin, Zixin Deng, Shukun Luo, Xudong Qu. Terminal carboxyl editing drives divergence in fasmacyin and anthrabenzoxocinone biosynthesis. J. Am. Chem. Soc. 2025, 147, 26468-26476.

  • Xiaoli Yan, Xinying Jia, Zhenyao Luo, Shunjia Ji, Meng-Jie Zhang, Hui Zhang, Mingjia Yu, Julie Orts, Kai Jiang, Zhi Lin, Zixin Deng, Xu-Dong Kong, Bostjan Kobe, Yi-Lei Zhao, Mehdi Mobli, Xudong Qu. An enzymatic dual-oxa Diels-Alder reaction constructs the oxygen-bridged tricyclic acetal unit of (-)-anthrabenzoxocinones. Nat. Chem. 2025, 17, 1058-1066.

  • Kai Jiang, Cheng Zhu, Xiaoli Yan, Guangjun Li, Zhi Lin, Ming Jiang, Zixin Deng, Shukun Luo, Xudong Qu. A stereoselective decarboxylative aromatase/cyclase directs the biosynthesis of an axially chiral biphenyl framework in fasamycin. J. Am. Chem. Soc. 2025, 147, 5596−5601.

  • Guangzheng Wei, Borui Duan, Tai-Ping Zhou, Wenya Tian, Chenghai Sun, Zhi Lin, Zixin Deng, Binju Wang, Zhengyu Zhang, Xudong Qu. A Nucleobase-driven P450 peroxidase system enables regio- and stereo-specific formation of C‒C and C‒N bonds. Proc. Natl. Acad. Sci. USA 2024, 121, e2412890121.

  • Kai Jiang, Xu Chen, Xiaoli Yan, Zixin Deng, Shunkun Luo, Xudong Qu. An unusual aromatase/cyclase programs the formation of the phenyldimethylanthrone framework in anthrabenzoxocinones and fasamycin. Proc. Natl. Acad. Sci. USA 2024, 121, e2321722121.

  • Chenghai Sun, Bao-Di Ma, Guangjun Li, Wenya Tian, Lu Yang, Haidong Peng, Zhi Lin, Zixin Deng, Xu-Dong Kong, Xudong Qu. Engineering the substrate specificity of a P450 dimerase enables the collective biosynthesis of heterodimeric tryptophan-containing diketopiperazines. Angew. Chem. Int. Ed. 2023, 62, e202304994.

  • Zhi Lin, Zhiwei Hu, Linjun Zhou, Benben Liu, Zixin Deng, Xudong Qu. A large conserved family of small molecule carboxyl methyltransferases identified from Microorganisms. Proc. Natl. Acad. Sci. USA 2023, 120, e2301389120.

  • Fuzhen Song, Mengmeng Zheng, Junlin Wang, Huanhuan Liu, Zhi Lin, Benben Liu, Zixin Deng, Hengjiang Cong, Qianghui Zhou, Xudong Qu. Chemoenzymatic synthesis of C14-functionalized steroids. Nat. Synth. 2023, 2, 729-739.

  • Chenghai Sun, Wenya Tian, Zhi Lin, Xudong Qu. Biosynthesis of pyrroloindoline-containing natural products. Nat. Prod. Rep. 2022, 39, 1721-1765.

  • Mengmeng Zheng, Jun Zhang, Wan Zhang, Lu Yang, Xiaoli Yan, Wenya Tian, Zhihao Liu, Zhi Lin, Zixin Deng, Xudong Qu. An atypical acyl-CoA synthetase enables efficient biosynthesis of extender units for engineering a polyketide carbon scaffold. Angew. Chem. Int. Ed. 2022, 61, e202208734.

  • Xiaoli Yan, Jun Zhang, Hongqun Tan, Zhihao Liu, Kai Jiang, Wenya Tian, Mengmeng Zheng, Zhi Lin, Zixin Deng, Xudong Qu. A Pair of atypical KAS III homologues with initiation and elongation functions programs the polyketide biosynthesis in asukamycin. Angew. Chem. Int. Ed. 2022, 61, e202200879.

  • Haidong Peng, Yaya Wang, Kai Jiang, Xinru Chen, Wenlu Zhang, Yanan Zhang, Zixin Deng, Xudong Qu. A dual role reductase from phytosterol catabolism enables efficient production of valuable steroid precursors. Angew. Chem. Int. Ed. 2021, 60, 5414-5420.

  • Chenghai Sun, Zhenyao Luo, Wenlu Zhang, Wenya Tian, Haidong Peng, Zhi Lin, Xiaoli Yan, Yanan Zhang, Zixin Deng, Bostjan Kobe, Xinying Jia, Xudong Qu. Molecular basis of regio- and stereo-specificity in biosynthesis of bacterial heterodimeric ketopiperazines. Nat. Commun. 2020, 11, 6251.

  • Lu Yang, Jinmei Zhu, Chenghai Sun, Zixin Deng, Xudong Qu. Biosynthesis of plant tetrahydroisoquinolines alkaloids through an imine reductase route. Chem. Sci. 2020, 11, 364-371 (2019 Chemical Science HOT Article Collection).

  • Junlin Wang, Yanan Zhang, Linjun Zhou, Linpeng Wei, Wenbing Yin, Zixin Deng, Xudong Qu, Qianghui Zhou. A biocatalytic hydroxylation-enabled unified approach to C19-hydroxylated steroids. Nat. Commun. 2019, 10, 3378.

  • Wenya Tian, Chenghai Sun, Mei Zheng, Mingjia Yu, Yanan Zhang, Haidong Peng, Dongqing Zhu, Jeffery Harmer, Zixin Deng, Shilu Chen, Mohedi Mobli, Xinying Jia, Xudong Qu. Efficient biosynthesis of heterodimeric C3-aryl pyrroloindoline alkaloids. Nat. Commun. 2018, 9, 4428.

  • Yuan Li, Wan Zhang, Hui Zhang, Wenya Tian, Lian Wu, Shuwen Wang, Jun Zhang, Chenghai Sun, Yuhui Sun, Zixin Deng, Xudong Qu, Jiahai Zhou. Structural basis of a broadly selective acyltransferase from the polyketide synthase of splenocin. Angew. Chem. Int. Ed. 2018, 57, 5823-5827.

  • Chengcheng Chang, Rong Huang, Yan Yan, Hongmin Ma, Zheng Dai, Benying Zhang, Wen Liu, Zixin Deng, Xudong Qu. Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into Polyketide carbon scaffolds. J. Am. Chem. Soc. 2015, 137, 4183-4190.

  • Qiongqiong Wu, Zhuhua Wu, Xudong Qu, Wen Liu. Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetramate/tetronate formation. J. Am. Chem. Soc. 2012, 134, 17342-17345.

  • Xudong Qu*, Bo Pang, Zicong Zhang, Ming Chen, Zhuhua Wu, Qunfei Zhao, Qinglin Zhang, Yingyan Wang, Yun Liu, Wen Liu*. Caerulomycins and collismycins share a common paradigm for 2, 2’-bipyridine biosynthesis via an unusual hybrid polyketide-peptide assembly logic. J. Am. Chem. Soc. 2012, 134, 9038-9041.