教授
天然產物是新藥研發的重要源泉，但其成藥潛力高度依賴於結構優化🫶🏽。復雜天然產物的碳骨架由於化學性質惰性，選擇性的結構修飾極具挑戰，而罕有實現；在藥物生產方面，一些非微生物來源的天然藥物，常需通過天然提取，或者高難度的全合成方法進行製造👩🏿，生產效率低下且成本高昂✊🏽🦂。因此🗣，如何開發普適🏝、高效的骨架修飾與合成方法，是化學領域的難點和熱點，亦是當前藥物在研發和生產兩端有待解決的瓶頸。本實驗室長期致力於天然產物骨架的高效構建和選擇性修飾這一科學問題，一方面從解析聚酮合酶體系催化合成💅🏽、組裝和環合碳鏈的核心分子機製出發，利用酶工程和合成生物學等手段對聚酮合酶催化合成碳鏈過程進行精準操控🪿，來實現對聚酮、生物堿等重要天然產物的定向生物合成以及骨架結構的精準修飾（Bottom-UP策略）🥻；另一方面采用Top-Down策略，從解析植物甾醇的生物降解機製出發，通過工程化手段精準控製微生物降解植物甾醇和修飾甾體骨架的過程，以廉價的植物甾醇為原料進行甾體藥物的高效合成和創新。通過生物合成與化學合成結合的方式，發展針對各類天然產物骨架的普適☯️、高效的合成與編輯策略🧑🏻🔧🧛🏻♀️，用於拓展結構多樣性和提高藥物的生產效率🏇🏽，實現對天然產物資源的深度開發及天然藥物的高效創製。
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 DOI: 10.1021/jacs.4c18376.
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 2024, accepted.
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.
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
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.
Angewandte Chemie International Edition 2022, e202208734..
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