副研究員
綜合運用基因工程、酶工程⚫️、代謝工程👨🏽🦱、生物信息學、化合物結構鑒定等多學科技術🔽，開展了井岡黴烯胺、井岡黴醇胺生物合成途徑設計、催化元件募集🐉、體外酶學催化實驗驗證🤦🏿♀️、體內途徑適配優化等系統工作👨🏽💼🥱，實現了II型糖尿病臨床治療藥物伏格列波糖前體化合物井岡黴烯胺🔙、井岡黴醇胺和GM1-神經節苷脂貯積症等治療藥物前體化合物β-井岡黴烯胺的設計合成，為C7N氨基環醇化合物生物製造開創了全新的思路🚵。
依據合成生物學設計理念，募集並表征了參與C7N氨基環醇類化合物的結構形成的環化酶、異構酶👓、脫水酶和氨基轉移酶🩱⬆️，建立了C7N氨基環醇類化合物組合生物合成元件庫和以糖苷酶抑製活力為指標的生物學功能高通量評價篩選方法🏄🏼♂️，為利用微生物代謝中多樣性酶催化功能🎆、依據化學與酶學催化反應原理👩💼🖋，設計全新非天然C7N藥物的人工生物合成途徑奠定了基礎。
依據酶活性、穩定性及底物選擇性等復雜催化機製，采用計算生物學輔助的酶理性設計策略，塑造和優化候選氨基轉移酶的催化功能，提升其催化非天然底物的效率和精準度；為改變天然酶對非天然底物的選擇性👿、提升酶與底物的識別能力🧇、實現特定催化功能提供了高效🚵♀️、準確的解決方案。
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
Liu Q, Guo X, Xun GH, Li ZL, Chong YS, Yang LT, Wang HX, Zhang FC, Luo SK, Cui L, Zhao PS, Ye XY, Xu HS, Lu H, Li X, Deng ZX, Li K, Feng Y*. Argonaute integrated single-tube PCR system enables supersensitive detection of rare mutations. Nucleic Acids Research, 2021, gkab274.
Wang RX†, Qiao L†, Liu MF†, Ran YP, Wang J, Yan WP, Feng Y, Cui L*. Development of an Engineered Sugar Aminotransferase with Simultaneously Improved Stability and Non-natural Substrate Activity for Synthesizing the Glucosidase Inhibitor Valienamine. Engineering, 2024, 42:185-195.
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