副研究员
依据酶活性、稳定性及底物选择性等复杂催化机制，采用计算生物学辅助的酶理性设计策略，塑造和优化候选氨基转移酶的催化功能，提升其催化非天然底物的效率和精准度；为改变天然酶对非天然底物的选择性、提升酶与底物的识别能力、实现特定催化功能提供了高效、准确的解决方案。
依据合成生物学设计理念，募集并表征了参与C7N氨基环醇类化合物的结构形成的环化酶、异构酶、脱水酶和氨基转移酶，建立了C7N氨基环醇类化合物组合生物合成元件库和以糖苷酶抑制活力为指标的生物学功能高通量评价筛选方法，为利用微生物代谢中多样性酶催化功能、依据化学与酶学催化反应原理，设计全新非天然C7N药物的人工生物合成途径奠定了基础。
综合运用基因工程、酶工程、代谢工程、生物信息学、化合物结构鉴定等多学科技术，开展了井冈霉烯胺、井冈霉醇胺生物合成途径设计、催化元件募集、体外酶学催化实验验证、体内途径适配优化等系统工作，实现了II型糖尿病临床治疗药物伏格列波糖前体化合物井冈霉烯胺、井冈霉醇胺和GM1-神经节苷脂贮积症等治疗药物前体化合物β-井冈霉烯胺的设计合成，为C7N氨基环醇化合物生物制造开创了全新的思路。
Li Cui*, Anqi Cui, Qitong Li, Lezhou Yang, Hao Liu, Wenguang Shao, and Yan FengMolecular Evolution of an Aminotransferase Based on Substrate–Enzyme Binding Energy Analysis for Efficient Valienamine Synthesis. ACS Catal. 2022, 12, 13703.
Cui L*, Wei XD, Wang XR, Bai LQ, Lin SJ, Feng Y*. A validamycin shunt pathway for valienamine synthesis in engineered Streptomyces hygroscopicus 5008. ACS Synthetic Biology, 2020, 9 (2), 294-303.
Li Cui, Ying Zhu, Xiaoqing Guan, Zixin Deng, Linquan Bai*, and Yan Feng*. De Novo Biosynthesis of β-Valienamine in Engineered Streptomyces hygroscopicus 5008. ACS Synth Biol, 2016, 5, 15-20.
Khatun MA, Hoque MA, Zhang Y, Lu T, Cui L, Zhou NY, Feng Y*. A bacterial consortium-based sensing system for detecting organophosphorus pesticides. Anal Chem, 2018, 90(17):10577-10584.
Li Cui, Xiaoqing Guan, Zhangmin Liu, Liuyin Fan, Qian Li, and Yan Feng*. A new precolumn derivatization for valienamine and beta-valienamine using o-phthalaldehyde to determine the epimeric purity by HPLC and application of this method to monitor enzymatic catalyzed synthesis of beta-valienamine. J Asian Nat Prod Res, 2017,19(4): 347-357.
Xiaofei Zhang, Yong Zhang, Guangyu Yang, Yuan Xie, Lishi Xu, Jiao An, Li Cui, Yan Feng*. Modulation of the thermostability and substrate specificity of Candida rugose lipase1 by altering the acyl-binding residue Gly414 at the α-helix-connecting bend. Enzyme Microb Technol, 2016, 82:34-41
Yuan Xie, Jiao An, Guangyu Yang, Geng Wu, Yong Zhang, Li Cui, Yan Feng*. Enhanced Enzyme Kinetic Stability by Increasing Rigidity within the Active Site. J Biol Chem, 2014, 289: 7994-8006
Yu Zhang, Jiao An, Wei Ye, Guangyu Yang, Zhigang Qian, Haifeng Chen, Li Cui, Yan Feng*. Enhancing the promiscuous phosphotriesterase activity of a thermostable lactonase (GkaP) for the efficient degradation of organophosphate pesticides. Appl Environ Microbiol, 2012, 78(18):6647-6655
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