杨广宇 的个人介绍页
杨广宇
杨广宇
副研究员
...
enzyme.sjtu.edu.cn
34205079

个人简历

2003年毕业于吉林大学生命科学学院生物科学专业;同年进入吉林大学分子酶学工程教育部重点实验室开始硕博连读,2007年11月-2008年11月在加拿大不列颠哥伦比亚大学进行联合培养,2009年6月获生物化学与分子生物学博士学位。2009年7月至今在上海交通大学生命科学技术学院工作,2013年晋升为副研究员。承担了生命学院《生物化学》、《蛋白质工程与应用》、《生物大分子结构与功能》的部分教学任务。
近年一直从事微生物酶学的研究工作,参与了多种重要代谢酶的克隆与表征、酶结构-功能研究、分子设计与定向进化等工作,作为项目负责人承担了自然科学基金、973子课题、教育部博士点基金、杰能科创新研究计划等科研项目,并作为主要成员参与了参与了多项国家973、863、自然科学基金项目的研究。在Angew Chemie, J Am Chem Soc, Anal Chem, J Lipid Research等杂志发表论文28篇(其中第一及通讯作者17篇),他引200余次,申请及授权专利9项。担任了Scientific Reports, Journal of Biotechnology, Enzyme and Microbial Technology, Process Biochemistry等10余个SCI杂志的审稿人。2010、2013、2016年分别获上海交通大学“SMC晨星学者优秀青年教师奖励计划(C类)、(B类)、(A类)”支持。2015年获上海交通大学“青年岗位能手”称号。
以“基于荧光激活细胞分选(FACS)的酶活性超高通量筛选技术开发与应用”为主题的报告在中国微生物学会2014年学术年会上获得了优秀论文奖,并受邀在中国微生物学会2015年学术年会的青年学者分会上作了主旨报告;还受邀在2015年第七届中日化工学术研讨会、2015年第四届生物育种暨高通量筛选会议、2015年第三届高效克隆筛选研讨会、2015年iBioK会议上作了邀请报告。

研究方向

主要围绕糖及脂类化合物合成及分解酶系这一主线,在酶催化机制解析、分子设计及改造、多酶耦合催化体系构建等方面开展了系统研究,形成了一定的研究特色。
1)酶功能及催化机制解析。对基因组文库进行深入挖掘,根据生物分子进化性分析,鉴定了新型嗜热木聚糖酶、鞘糖脂N-去酰化酶及鞘糖脂内切糖苷酶,为生物质降解及鞘糖脂类药物合成提供了优质的酶源(J Mol Cata B: Enzym. 2015;Appl Microbiol Biot 2015);发现酶结构中loop区对酶催化和蛋白质稳定性的调节作用;对loop区热点区域的优化,成功地将内酯酶转变为磷酸三酯酶(PloS One. 2012;PloS One 2015)。
2)酶分子设计与功能优化。针对酶定向进化中的高通量筛选瓶颈问题,建立了酶“微反应器-FACS (IVC-FACS)”超高通量筛选技术平台,成功地实现了酶催化活性的快速定向进化 (PloS One. 2014, Anal Chem, 2016);应用“酶活性中心稳定化”策略,即针对酶活性中心区域柔性较高、构象易变的特点,通过定向结构修饰来提高其刚性,显著提升了重要的工业脂肪酶CalB的动力学稳定性(J Biol Chem. 2014;Enzyme Microb Tech. 2016);
3) 体外合成生物学催化体系的构建。依据合成生物学原理,设计并建立了鞘糖脂合成的多酶耦合合成体系;针对天然酶活性检测困难的问题,设计合成了鞘糖脂代谢酶通用型FRET荧光探针,分别在体外检测、细胞膜表面酶原位分析、高通量筛选中证明了该探针的应用,为鞘糖脂类的代谢和生理功能研究提供了重要研究工具 (Angew. Chemie. 2015)。通过反应体系优化,将鞘糖脂合成中的关键步骤鞘糖脂N-去酰基化酶的转化率从40%提高至96%,极大的提升了鞘糖脂类的合成效率(J Lipid Research. 2015)。

发表论文

1) Fuqiang Ma, Yuan Xie, Manjie Luo, Shuhao Wang, You Hu, Yukun Liu, Yan Feng, Guang-Yu Yang*. Sequence Homolog-based Molecular Engineering for Shifting the Enzymatic pH Optimum. Synthetic and Systems Biotechnology, 2016, in press
2) Fuqiang Ma, Michael Fischer, Yunbin Han, Stephen G. Withers, Yan Feng, Guang-Yu Yang*. Substrate engineering enabling fluorescence droplet entrapment for IVC-FACS-based ultrahigh-throughput screening. Anal Chem, 2016, 88, 8587−8595
3) Xiao-Fei Zhang, Guang-Yu Yang, Yong Zhang, Yuan Xie, Stephen G. Withers, Yan Feng, A general and efficient strategy for generating the stable enzymes. Scientific Reports, 2016, in press
4) 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 rugosa lipase1 by altering the acyl-binding residue Gly414 at the α-helix-connecting bend. Enzyme and Microbial Technology. 2016, 82, 34-41.
5) FT Huang, YB Han, Y Feng, GY Yang*. A facile method for controlling the reaction equilibrium of sphingolipid ceramide N-deacylase for lyso-glycosphingolipid production. Journal of lipid research. 2015, 56(9):1836-42.
6) J An, Y Xie, Y Zhang, D Tian, S Wang, G Yang*, Y Feng*. Characterization of a thermostable, specific GH10 xylanase from Caldicellulosiruptor bescii with high catalytic activity. Journal of Molecular Catalysis B: Enzymatic. 2015, 117, 13-20.
7) Guang-Yu Yang, Caishun Li, Michael Fischer, Christopher W. Cairo, Yan Feng, Stephen G. Withers. A FRET Probe for Cell-Based Imaging of Ganglioside-Processing Enzyme Activity and High-Throughput Screening. Angew. Chemie. 2015, 54(18):5389-93
8) Yun-Bin Han, Lie Wu, Jamie R. Rich, Feng-Tao Huang, Stephen G. Withers, Yan Feng, Guang-Yu Yang*. Comprehensive Characterization of Sphingolipid Ceramide N-deacylase for the Synthesis and Fatty Acid Remodeling of Glycosphingolipids. Applied Microbiology and Biotechnology. 2015, 99(16):6715-26.
9) Yu Zhang**, Jiao An**, Guangyu Yang**, Aixi Bai, Baisong Zheng, Zhiyong Lou, Geng Wu, Wei Ye, Haifeng Chen, Yan Feng*, Giuseppe Manco* Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426 PloS One 2015, e0115130. (**equal contribution)
10) Xiaoli Zhou, Le Gao, Guangyu Yang, Donglai Liu, Aixi Bai, Binchun Li, Zixin Deng, Yan Feng* Design of hyperthermophilic lipase chimeras by key motif-directed recombination Chembiochem. 2015, 16, 455-462
11) Yuan Xie, Jiao An, Guangyu Yang, Geng Wu, Yan Feng*. Enhanced enzyme kinetic stability by increasing rigidity within the active site. J. Biol. Chem. 2014, 289, 7994-8006.
12) Fuqiang Ma, Yuan Xie, Chen Huang, Yan Feng, Guangyu Yang*. An improved single cell ultrahigh throughput screening met·hod based on in vitro compartmentalization. PloS One. 2014, 9(2): e89785.
13) 罗漫杰,谢渊,钱志刚,冯雁,杨广宇*。超嗜热酯酶EST2在不同宿主中的异源高效表达研究。中国生物工程杂志,2014, 34(12), 36-44.
14) 施贤卫,张伟涛,张小飞,杨广宇,冯雁*。Actinosynnema mirum DSM 43827溶解性多糖单加氧酶的异源表达和酶学性质表征,中国生物工程杂志, 2014, 34(7):17-23.
15) Aixi Bai, Xinyu Zhao, Yanwei Jin, Guangyu Yang, Yan Feng. A novel thermophilic β-glucosidase from Caldicellulosiruptor bescii: characterization and its synergistic catalysis with other cellulases. Journal of Molecular Catalysis B: Enzymatic. 2013, 85-86, 248-256.
16) Binchun Li**, Guangyu Yang**, Lie Wu, Yan Feng. Role of the NC-loop in Catalytic Activity and Stability in Lipase from Fervidobacterium changbaicum. PloS One. 2012, 7(10), e46881. (**equal contribution)
17) Yuexi Wang, Binchun Li, Weiwei Han, Guangyu Yang, Zuoming Zhang, Yan Feng. Redesigning the active site of a carboxyl esterase from the archaeon Archaeoglobus fulgidus to improve sensitivity to organophosphorus compounds. Process Biochemistry. 2012, 47(12), 2219–2226.
18) Yu Zhang, Jiao An, Wei Ye, Guangyu Yang, Zhi-Gang Qian, Hai-Feng 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.
19) 马富强,冯雁,杨广宇*。荧光激活细胞分选超高通量酶活性筛选方法及其应用, 生物化学与生物物理进展,2012, 39(4): 299~306.
20) Chang Liu**, Guangyu Yang**, Lie Wu, Guohe Tian, Zuoming Zhang, Yan Feng*. Switch of substrate specificity of hyperthermophilic acylaminoacyl peptidase by combination of protein and solvent engineering. Protein & Cell. 2011, 6, 497-506. (**equal contribution)

21) Guangyu Yang, Jamie R. Rich, Michel Gilbert, Warren W. Wakarchuk, Yan Feng, Stephen G. Withers. Fluorescence Activated Cell Sorting as a General Ultra High-throughput Screening Method for Directed Evolution of Glycosyltransferases. J. Am. Chem. Soc., 2010,132(30):10570-10577.
22) Guangyu Yang, Aixi Bai, Yan Feng. Molecular Redesign and Construction of New Biocatalysts. Current Organic Chemistry, 2010, 14(14): 1407-1423.
23) 杨广宇,冯雁。合成生物学中的酶定向进化与模块组装,《生物产业技术》2010, 5: 36-43。
24) Guangyu Yang, Stephan G Withers. Ultrahigh-throughput FACS-based screening for directed enzyme evolution. Chembiochem. 2009, 10(17), 2704-2715.
25) Guangyu Yang, Aixi Bai, Le Gao, Zuoming Zhang, Baisong Zheng, Yan Feng. Glu88 in the non-catalytic domain of acylpeptide hydrolase plays dual roles: Charge neutralization for enzymatic activity and formation of salt bridge for thermodynamic stability. Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics, 2009, 1794, 94-102.
26) Qiuyan Wang, Guangyu Yang, Yanli Liu, Yan Feng. Discrimination of esterase and peptidase activities of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 by a Single Mutation. J. Biol. Chem. 2006, 281, 18618–18625.
27) 刘艳莉,杨广宇,王秋岩,冯雁。脂肪酶和酯酶的定向进化及其应用。生物加工过程,2006年,4:16-20.
28) 王秋岩,杨广宇,刘艳莉,王艳平,冯雁。嗜热酯酶APE1547催化活性的定向进化研究,微生物学报,2005,46:259-262.

研究成果

专利授权及申请:
1. 冯雁,张宇,安娇,杨广宇,磷酸三酯酶突变体及其制备方法和应用(ZL201210015196.2)
2. 冯雁,谢渊,杨广宇,热稳定性提高的脂肪酶突变体及其构建方法(ZL201110406922.9)
3. 冯雁,郑翠红,杨广宇,白挨玺,李彬春,嗜热羧酸酯酶基因工程菌的构建及其酶的应用(ZL201110406844.2)
4. 杨广宇、冯雁、黄锋涛、韩云宾,一种酶法高效水解鞘脂制备溶血鞘脂的方法(申请号:201410508221.x)
5. 杨广宇、冯雁、庄宇,一种糖基转移酶及其突变体在合成人参皂苷Rh2中的应用(申请号: 201410534597.8)
6. 杨广宇、冯雁、安娇、于瑶;王慧楠、张少博,一种基因工程木聚糖酶及其制备与应用(申请号:201410534600.6)