特聘教授
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。
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.
Nature Chemistry 2025, 17, 1058-1066.
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.
Nature Communications 2025, in press.
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.
Journal of the American Chemical Society 2025, 147, 5596-5601.
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.
Journal of the American Chemical Society 2025, 147, 26468-26476.
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.
Proceedings of the National Academy of Sciences of the United States of America 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.
Proceedings of the National Academy of Sciences of the United States of America 2024, 121, e2321722121.
Fuzheng Song, Mengmeng Zheng, Junlin Wang, Huanhuan Liu, Zhi Lin, Bengbeng Liu, Zixin Deng, Qianghui Zhou, Xudong Qu. A chemoenzymatic approach to C14-functionalized steroids.
Nature Synthesis 2023, 2, 729-739.
Zhi Lin, Zhiwei Hu, Linjun Zhou, Benben Liu, Xiaowei Huang, Zixin Deng, Xudong Qu.
A large conserved family of small-molecule carboxyl methyltransferases identified from microorganisms.
Proceedings of the National Academy of Sciences of the United States of America, 2023, 120, e2301389120.
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.
Angewandte Chemie International Edition 2023, 62, e202304994.
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.
Angewandte Chemie International Edition 2022, e202200879
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