Xudong Qu

Professor

  • Tel: +86-021
  • Email: quxd19@sjtu.edu.cn
  • Address: Rm. 2-509, Zhang Jiang Institute of Advanced Study, Pudong District

Education and Research Experience

  • 2020-present, Professor, Shanghai Jiao Tong University, School of Life Sciences and Biotechnology, China.
  • 2012-2020 Professor, Wuhan University, School of Pharmaceutical Sciences, China.
  • 2011-2011 Associate Investigator, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
  • 2008-2010 Assistant Investigator, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
  • 2007-2008 Post-doctoral Associate, Massachusetts Institute of Technology, Department of Chemistry, USA.
  • 2002-2007 PhD, Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China.
  • 1998-2002 BS, Chemistry, East China Normal University, China.

Research Interests

Biosynthesis of inert molecular scaffolds

   Pharmaceuticals are indispensable for human survival, but there has been a long-term inssued bottleneck at both ends of drug development and production, that is, the efficient synthesis and engineering of the carbon scaffold. Structural modification is pivotal for development of natural products-derived drugs (NPD drugs). It is known that about 90% of NPD drugs have been structurally optimized. However, due to the limitation of chemical reactivity, chemical modification is usually only applicable to active functional groups (such as hydroxyl, amino, etc.), and rarely to the scaffold part composed of saturated carbon atoms (inert scaffold). Therefore, the inert carbon scaffold, which accounts for around half of the molecular scaffold, has always been a forbidden area for the development of new drugs. Hence, developing efficient and universal modification approaches to engineer them in natural products is of great significance to the development of NPD drugs.  In drug production, chiral chemical catalysts are usually very expensive and difficult to be used in large-scale production, so current pharmaceutical industry still mainly relies on chiral resolution to obtain chiral drugs. This process is uneconomical, unsustainable and easy to form wastes, therefore development of efficient biosynthetic approaches to stereo-specifically making chiral carbon scaffolds is of great significance for industrial production of pharmaceuticals. The research direction of our group is 'biosynthesis of inert molecular scaffolds'. We focus on three important  scaffold types, including polyketides, steroids and azacycles which constitute nearly 100,000 natural products and more than 1500 clinical drugs. Our aim is to i) understand the formation of these molecular scaffolds in natural products, and ii) to develop efficient and universal biosynthetic approaches to engineer or synthesis of these  scaffolds. With our efforts, we wish to solve this long-standing bottleneck in the drug development and production.

Selected Publications

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    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.

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    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.

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    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.

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    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.

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    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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    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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    Haidong Peng, Yaya Wang, Yanan Zhang, Zixing Deng, Zhenghua Tian, Xudong Qu.

    A dual role reductase from phytosterol catabolism enables efficient production of valuable
    steroid precursors.

    Angewandte Chemie International Edition 2021, 60, 5414-5420.

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    Chenghai Sun, Zhenyao Luo (co-first author), 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.

    Nature Communications 2020, 11, 6251.

     

    •  

    Wenya Tian, Chenghai Sun (co-first author), 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.

    Nature Communications 2018, 9, 4428.

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    Chengcheng Chang, Rong Huang (co-first author), 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.

    Journal of the American Chemical Society 2015, 137, 4183-4190.

Academic Rewards

  • 2014 National Science Foundation for Excellent Young Scholars
  • 2013 New Century Excellent Talents in University, Chinese Ministry of Education
  • 2012 Luojia Distinguished Professor of Wuhan University

Teaching Experiences

  • 2012-2019,Undergraduate Course, Chemical Biology (Wuhan University)
  • 2012-2019,Graduate Course, Proceedings of Biological Pharmacetucial Sciences (Wuhan University)
  • National Natural Science Foundation of China-31970054, 2020-2023, PI
  • National Key R&D Project-2018YFC1706200, 2018-2021, Co-PI
  • National Key R&D Project-2018YFA090038, 2019-2024, Co-PI
  • National Natural Science Foundation of China-31770063, 2018-2021, PI
  • National Natural Science Foundation of China-31570057, 2016-2019, PI
  • National Science Foundation for Excellent Young Scholars-31322002, 2014-2016, PI
  • National Natural Science Foundation of China-31270119, 2013-2016, PI
  • New Century Excellent Talents in University, Chinese Ministry of Education-NCET-12-0423, 2013-2015, PI
  • National Natural Science Foundation of China-30900021, 2010-2012, PI

Selected Grants