基本信息

朱蕾蕾  女  博导  中国科学院天津工业生物技术研究所
电子邮件: zhu_ll@tib.cas.cn
通信地址: 天津空港经济区西七道32号
邮政编码: 300308

研究领域

  聚焦酶元件进化设计与绿色生物制造领域,致力于发展先进的酶分子改造方法和高通量筛选技术,采用定向进化和半理性设计等手段创制高性能的工业酶和蛋白质,使其获得新属性或提高固有属性;开发简短绿色的化学品合成路径,高效利用可再生廉价替代原料(如:一碳化合物),推动化学品的绿色生物制造;在总结大量实验数据的基础上,从分子水平提炼影响酶/蛋白质特性的一般性规律,结合人工智能手段,为提高工业酶和蛋白质的应用水平提供必要的理论支撑。


招生信息

招生专业
071010-生物化学与分子生物学
招生方向
蛋白质工程

教育背景

2009-07--2010-09   亚琛工业大学(RWTH Aachen University)   博士学位
2007-07--2009-06   不来梅雅各布大学 (Jacobs University Bremen)   博士学习
2005-09--2007-06   江南大学   硕士学位
2001-09--2005-06   江南大学   本科学位
学历

博士


学位
博士

工作经历

2016-08~现在, 中国科学院天津工业生物技术研究所, 研究组长
2011-01~2016-07,亚琛工业大学 (RWTH Aachen University), 研究小组组长 (Subgroup leader)


工作简历
2016-09~现在, 中国科学院天津工业生物技术研究所, 研究组长
2011-01~2016-07,亚琛工业大学 (亚琛工业大学), 研究小组组长 (Subgroup leader)

专利与奖励

   
专利成果
[1] 朱蕾蕾. 一种耐受表面活性剂的脂肪酶变体. 202210198070.7, 2022-03-01.

[2] 朱蕾蕾, 聂志华. 一种赖氨酸外排蛋白及其应用. 202210065236.8, 2022-01-20.

[3] 朱蕾蕾, 李天真, 唐梓静, 谭子瑊, 马延和. 甲醛转化突变蛋白及其应用. CN: CN113832120A, 2021-12-24.

[4] 朱蕾蕾, 聂志华. 一种谷氨酸外排蛋白突变体及其应用. CN: CN113493500A, 2021-10-12.

[5] 朱蕾蕾, 聂志华. 一种生产L-谷氨酸的方法. CN: CN113135985A, 2021-07-20.

[6] 朱蕾蕾, 唐梓静, 蔡韬, 谭子瑊, 孙红兵, 马延和. 一种甲醛转化蛋白及其应用. CN: CN113122525A, 2021-07-16.

[7] 朱蕾蕾, 李天真, 谭子瑊, 唐梓静. 一种合成乳酸的方法. CN: CN112852766A, 2021-05-28.

[8] 朱蕾蕾, 石利霞, 高松枫. 一种信号肽突变体及其应用. CN: CN112852800A, 2021-05-28.

[9] 朱蕾蕾, 成超. 一种溶解性多糖单加氧酶突变体及其应用. CN: CN112442488A, 2021-03-05.

[10] 朱蕾蕾. 抗癌药物精氨酸脱亚胺酶半衰期的分子改造方法及突变株. CN: CN109652400A, 2019-04-19.

[11] 孙志浩, 郑 璞, 刘宇鹏, 朱蕾蕾. 一种微生物发酵生产丁二酸的菌种和方法. CN: CN1814747A, 2006-08-09.

出版信息

   
发表论文
[1] Shi, Lixia, Liu, Pi, Tan, Zijian, Zhao, Wei, Gao, Junfei, Gu, Qun, Ma, Hongwu, Liu, Haifeng, Zhu, Leilei. Complete Depolymerization of PET Wastes by an Evolved PET Hydrolase from Directed Evolution. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2023, http://dx.doi.org/10.1002/anie.202218390.
[2] Su, Xiaolan, Yang, Jianhua, Yuan, Huiling, Liu, Cui, Tu, Ran, Liu, Pi, Wang, Qinhong, Zhu, Leilei. Directed Evolution of Laccase for Improved Thermal Stability Facilitated by Droplet-Based Microfluidic Screening System. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY. 2022, [3] Li, Tianzhen, Tan, Zijian, Tang, Zijing, Liu, Pi, Liu, Haifeng, Zhu, Leilei, Ma, Yanhe. One-pot chemoenzymatic synthesis of glycolic acid from formaldehyde. GREEN CHEMISTRY[J]. 2022, 24(13): 5064-5069, http://dx.doi.org/10.1039/d2gc00688j.
[4] Ren, Pengju, Tan, Zijian, Zhou, Yingying, Tang, Hongzhi, Xu, Ping, Liu, Haifeng, Zhu, Leilei. Biocatalytic CO2 fixation initiates selective oxidative cracking of 1-naphthol under ambient conditions. GREEN CHEMISTRY[J]. 2022, 24(12): 4766-4771, http://dx.doi.org/10.1039/d2gc01226j.
[5] Yang, Jianhua, Tu, Ran, Yuan, Huiling, Wang, Qinhong, Zhu, Leilei. Recent advances in droplet microfluidics for enzyme and cell factory engineering. CRITICAL REVIEWS IN BIOTECHNOLOGYnull. 2021, 41(7): 1023-1045, http://dx.doi.org/10.1080/07388551.2021.1898326.
[6] Nie, Zhihua, Liu,Pi, Zheng, Ping, Zhu, Leilei. Directed evolution and rational design of mechanosensitive channel MscCG2 for improved glutamate excretion efficiency. Journal of Agricultural and Food Chemistry[J]. 2021, [7] Shi, Lixia, Liu, Haifeng, Gao, Songfeng, Weng, Yunxuan, Zhu, Leilei. Enhanced Extracellular Production of IsPETase in Escherichia coli via Engineering of the pelB Signal Peptide. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY[J]. 2021, 69(7): 2245-2252, http://dx.doi.org/10.1021/acs.jafc.0c07469.
[8] Cai, Tao, Sun, Hongbing, Qiao, Jing, Zhu, Leilei, Zhang, Fan, Zhang, Jie, Tang, Zijing, Wei, Xinlei, Yang, Jiangang, Yuan, Qianqian, Wang, Wangyin, Yang, Xue, Chu, Huanyu, Wang, Qian, You, Chun, Ma, Hongwu, Sun, Yuanxia, Li, Yin, Li, Can, Jiang, Huifeng, Wang, Qinhong, Ma, Yanhe. Cell-free chemoenzymatic starch synthesis from carbon dioxide. SCIENCE[J]. 2021, 373(6562): 1523-+, http://apps.webofknowledge.com/CitedFullRecord.do?product=UA&colName=WOS&SID=5CCFccWmJJRAuMzNPjj&search_mode=CitedFullRecord&isickref=WOS:000698977800053.
[9] Guo, Wenzhu, Yang, Jianhua, Huang, Tianchen, Liu, Dandan, Liu, Qian, Li, Jingen, Sun, Wenliang, Wang, Xingji, Zhu, Leilei, Tian, Chaoguang. Synergistic effects of multiple enzymes from industrial Aspergillus niger strain O1 on starch saccharification. BIOTECHNOLOGY FOR BIOFUELS[J]. 2021, 14(1): http://dx.doi.org/10.1186/s13068-021-02074-x.
[10] 杨建花, 苏晓岚, 朱蕾蕾. 高通量筛选系统在定向改造中的新进展. 生物工程学报[J]. 2021, 37(7): 2197-2210, http://lib.cqvip.com/Qikan/Article/Detail?id=7105409049.
[11] 李燕, 杨建花, 李宝库, 朱蕾蕾. 漆酶-介体系统对多种不同结构染料的脱色效果. 环境工程学报[J]. 2020, 14(12): 3308-3316, http://lib.cqvip.com/Qikan/Article/Detail?id=7103727345.
[12] Cheng, Chao, Haider, Junaid, Liu, Pi, Yang, Jianhua, Tan, Zijian, Huang, Tianchen, Lin, Jianping, Jiang, Min, Liu, Haifeng, Zhu, Leilei. Engineered LPMO Significantly Boosting Cellulase-Catalyzed Depolymerization of Cellulose. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY[J]. 2020, 68(51): 15257-15266, https://www.webofscience.com/wos/woscc/full-record/WOS:000603399600020.
[13] 石利霞, 高松枫, 朱蕾蕾. PET水解酶的研究进展. 生物技术通报[J]. 2020, 36(10): 226-236, http://lib.cqvip.com/Qikan/Article/Detail?id=7103088614.
[14] Li, Tianzhen, Tang, Zijing, Wei, Hongli, Tan, Zijian, Liu, Pi, Li, Jinlong, Zheng, Yingying, Lin, Jianping, Liu, Weidong, Jiang, Huifeng, Liu, Haifeng, Zhu, Leilei, Ma, Yanhe. Totally atom-economical synthesis of lactic acid from formaldehyde: combined bio-carboligation and chemo-rearrangement without the isolation of intermediates. GREEN CHEMISTRY[J]. 2020, 22(20): 6809-6814, https://www.webofscience.com/wos/woscc/full-record/WOS:000579757000011.
[15] 聂志华, 朱蕾蕾. 生物素对发酵过程中MscCG外排L-谷氨酸的影响. 生物技术通报[J]. 2020, 36(10): 150-155, http://lib.cqvip.com/Qikan/Article/Detail?id=7103088605.
[16] 李燕, 杨建花, 李宝库, 朱蕾蕾. 定向进化转录调节基因提高漆酶异源表达. 山东化工[J]. 2020, 49(9): 26-28, http://lib.cqvip.com/Qikan/Article/Detail?id=7102048970.
[17] Anand, Deepak, Dhoke, Gaurao V, Gehrmann, Julia, Garakani, Tayebeh M, Davari, Mehdi D, Bocola, Marco, Zhua, Leilei, Schwaneberg, Ulrich. Chiral separation of D/L-arginine with whole cells through an engineered FhuA nanochannel. CHEMICAL COMMUNICATIONS[J]. 2019, 55(38): 5431-5434, https://www.webofscience.com/wos/woscc/full-record/WOS:000468369900029.
[18] Garakani, Tayebeh Mirzaei, Liu, Zhanzhi, Glebe, Ulrich, Gehrmann, Julia, Lazar, Jaroslav, Mertens, Marie Anna Stephanie, Moeller, Mieke, Hamzelui, Niloofar, Zhu, Leilei, Schnakenberg, Uwe, Boeker, Alexander, Schwaneberg, Ulrich. In Situ Monitoring of Membrane Protein Insertion into Block Copolymer Vesicle Membranes and Their Spreading via Potential-Assisted Approach. ACS APPLIED MATERIALS & INTERFACES[J]. 2019, 11(32): 29276-29289, https://www.webofscience.com/wos/woscc/full-record/WOS:000481567100075.
[19] Liu, Haifeng, Zhu, Leilei, Wallraf, AnneMaria, Raeuber, Christoph, Grande, Philipp M, Anders, Nico, Gertler, Christoph, Werner, Bernd, Klankermayer, Juergen, Leitner, Walter, Schwaneberg, Ulrich. Depolymerization of Laccase-Oxidized Lignin in Aqueous Alkaline Solution at 37 degrees C. ACS SUSTAINABLE CHEMISTRY & ENGINEERING[J]. 2019, 7(13): 11150-11156, http://dx.doi.org/10.1021/acssuschemeng.9b00204.
[20] Cheng, Feng, Yang, Jianhua, Schwaneberg, Ulrich, Zhu, Leilei. Rational surface engineering of an arginine deiminase (an antitumor enzyme) for increased PEGylation efficiency. BIOTECHNOLOGY AND BIOENGINEERING[J]. 2019, 116(9): 2156-2166, [21] Wallraf, AnneMaria, Liu, Haifeng, Zhu, Leilei, Khalfallah, Ghazi, Simons, Christian, Alibiglou, Hoda, Davari, Mehdi D, Schwaneberg, Ulrich. A loop engineering strategy improves laccase lcc2 activity in ionic liquid and aqueous solution. GREEN CHEMISTRY[J]. 2018, 20(12): 2801-2812, https://www.webofscience.com/wos/woscc/full-record/WOS:000435574300013.
[22] Cheng, Feng, Yang, Jianhua, Bocola, Marco, Schwaneberg, Ulrich, Zhu, Leilei. Loop engineering reveals the importance of active-site-decorating loops and gating residue in substrate affinity modulation of arginine deiminase (an anti-tumor enzyme). BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS[J]. 2018, 499(2): 233-238, http://dx.doi.org/10.1016/j.bbrc.2018.03.134.
[23] Grimm, Alexander R, Sauer, Daniel F, Polen, Tino, Zhu, Leilei, Hayashi, Takashi, Okuda, Jun, Schwaneberg, Ulrich. A Whole Cell E. coli Display Platform for Artificial Metalloenzymes: Poly(phenylacetylene) Production with a Rhodium-Nitrobindin Metalloprotein. ACS CATALYSIS[J]. 2018, 8(3): 2611-2614, https://www.webofscience.com/wos/woscc/full-record/WOS:000426804100111.
[24] Zhao, Jing, FrauenkronMachedjou, Victorine Josiane, Fulton, Alexander, Zhu, Leilei, Davari, Mehdi D, Jaeger, KarlErich, Schwaneberg, Ulrich, Bocola, Marco. Unraveling the effects of amino acid substitutions enhancing lipase resistance to an ionic liquid: a molecular dynamics study. PHYSICAL CHEMISTRY CHEMICAL PHYSICS[J]. 2018, 20(14): 9600-9609, http://dx.doi.org/10.1039/c7cp08470f.
[25] 朱蕾蕾. 3. A Whole Cell E. coli Display Platform for Artificial Metalloenzymes: Poly(phenylacetylene) Production with a Rhodium–Nitrobindin Metalloprotein. ACS Catalysis. 2018, [26] FrauenkronMachedjou, Victorine Josiane, Fulton, Alexander, Zhao, Jing, Weber, Lina, Jaeger, KarlErich, Schwaneberg, Ulrich, Zhu, Leilei. Exploring the full natural diversity of single amino acid exchange reveals that 40- 60% of BSLA positions improve organic solvents resistance. BIORESOURCES AND BIOPROCESSING[J]. 2018, 5(1): https://doaj.org/article/31e9d1d826a94dc7a5f6972aa8e428c1.
[27] Grimm, Alexander R, Sauer, Daniel F, Davari, Mehdi D, Zhu, Leilei, Bocola, Marco, Kato, Shunsuke, Onoda, Akira, Hayashi, Takashi, Okuda, Jun, Schwaneberg, Ulrich. Cavity Size Engineering of a beta-Barrel Protein Generates Efficient Biohybrid Catalysts for Olefin Metathesis. ACS CATALYSIS[J]. 2018, 8(4): 3358-+, https://www.webofscience.com/wos/woscc/full-record/WOS:000430154100082.
[28] 朱蕾蕾. 4. Cavity size engineering of a beta-barrel protein generates efficient biohybrid catalysts for olefin metathesis. ACS Catalysis. 2018, [29] Zhao, Jing, FrauenkronMachedjou, Victorine Josiane, Kardashliev, Tsvetan, Ruff, Anna Joelle, Zhu, Leilei, Bocola, Marco, Schwaneberg, Ulrich. Amino acid substitutions in random mutagenesis libraries: lessons from analyzing 3000 mutations. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY[J]. 2017, 101(8): 3177-3187, http://dx.doi.org/10.1007/s00253-016-8035-1.
[30] Markel, Ulrich, Zhu, Leilei, FrauenkronMachedjou, Victorine Josiane, Zhao, Jing, Bocola, Marco, Davari, Mehdi D, Jaeger, KarlErich, Schwaneberg, Ulrich. Are Directed Evolution Approaches Efficient in Exploring Nature's Potential to Stabilize a Lipase in Organic Cosolvents?. CATALYSTS[J]. 2017, 7(5): https://www.webofscience.com/wos/woscc/full-record/WOS:000404099100017.
[31] Himanshu Charan, Julia Kinzel, Ulrich Glebe, Deepak Anand, Tayebeh Mirzaei Garakani, Leilei Zhu, Marco Bocola, Ulrich Schwaneberg, Alexander Böker. Grafting PNIPAAm from β-barrel shaped transmembrane nanopores. BIOMATERIALS. 2016, 107: 115-123, http://dx.doi.org/10.1016/j.biomaterials.2016.08.033.
[32] Cheng, Feng, Zhu, Leilei, Lue, Hongqi, Bernhagen, Juergen, Schwaneberg, Ulrich. Directed arginine deiminase evolution for efficient inhibition of arginine-auxotrophic melanomas. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY[J]. 2015, 99(3): 1237-1247, https://www.webofscience.com/wos/woscc/full-record/WOS:000348771400019.
[33] Sauer, Daniel F, Bocola, Marco, Broglia, Claudio, Arlt, Marcus, Zhu, LeiLei, Brocker, Melanie, Schwaneberg, Ulrich, Okuda, Jun. Hybrid Ruthenium ROMP Catalysts Based on an Engineered Variant of beta-Barrel Protein FhuA Delta CVFtev : Effect of Spacer Length. CHEMISTRY-AN ASIAN JOURNAL[J]. 2015, 10(1): 177-182, https://www.webofscience.com/wos/woscc/full-record/WOS:000346736100024.
[34] Cheng, Feng, Zhu, Leilei, Schwaneberg, Ulrich. Directed evolution 2.0: improving and deciphering enzyme properties. CHEMICAL COMMUNICATIONS[J]. 2015, 51(48): 9760-9772, https://www.webofscience.com/wos/woscc/full-record/WOS:000355631700001.
[35] Cheng, Feng, Kardashliev, Tsvetan, Pitzler, Christian, Shehzad, Aamir, Lue, Hongqi, Bernhagen, Juergen, Zhu, Leilei, Schwaneberg, Ulrich. A Competitive Flow Cytometry Screening System for Directed Evolution of Therapeutic Enzyme. ACS SYNTHETIC BIOLOGY[J]. 2015, 4(7): 768-775, https://www.webofscience.com/wos/woscc/full-record/WOS:000358398100001.
[36] FrauenkronMachedjou, Victorine Josiane, Fulton, Alexander, Zhu, Leilei, Anker, Carolin, Bocola, Marco, Jaeger, KarlErich, Schwaneberg, Ulrich. Towards Understanding Directed Evolution: More than Half of All Amino Acid Positions Contribute to Ionic Liquid Resistance of Bacillus subtilis Lipase A. CHEMBIOCHEM[J]. 2015, 16(6): 937-945, https://www.webofscience.com/wos/woscc/full-record/WOS:000352489300008.
[37] Zhu, Leilei, Cheng, Feng, Piatkowski, Victoria, Schwaneberg, Ulrich. Protein Engineering of the Antitumor Enzyme PpADI for Improved Thermal Resistance. CHEMBIOCHEM[J]. 2014, 15(2): 276-283, https://www.webofscience.com/wos/woscc/full-record/WOS:000329877400013.
[38] Liu, Haifeng, Zhu, Leilei, Bocola, Marco, Chen, Nora, Spiess, Antje C, Schwaneberg, Ulrich. Directed laccase evolution for improved ionic liquid resistance. GREEN CHEMISTRY[J]. 2013, 15(5): 1348-1355, https://www.webofscience.com/wos/woscc/full-record/WOS:000318296700036.
[39] Zhu, Leilei, Tee, Kang Lan, Roccatano, Danilo, Sonmez, Burcu, Ni, Ye, Sun, ZhiHao, Schwaneberg, Ulrich. Directed Evolution of an Antitumor Drug (Arginine Deiminase PpADI) for Increased Activity at Physiological pH. CHEMBIOCHEM[J]. 2010, 11(5): 691-697, https://www.webofscience.com/wos/woscc/full-record/WOS:000276536000012.
[40] Zhu, Leilei, Verma, Rajni, Roccatano, Danilo, Ni, Ye, Sun, ZhiHao, Schwaneberg, Ulrich. A Potential Antitumor Drug (Arginine Deiminase) Reengineered for Efficient Operation under Physiological Conditions. CHEMBIOCHEM[J]. 2010, 11(16): 2294-2301, https://www.webofscience.com/wos/woscc/full-record/WOS:000284050800012.
[41] 刘宇鹏, 朱蕾蕾, 郑璞, 倪晔, 孙志浩. 琥珀酸发酵高产菌株的选育. 工业微生物[J]. 2007, 37(2): 1-6, http://lib.cqvip.com/Qikan/Article/Detail?id=24238662.
[42] 郑璞, 朱蕾蕾, 刘宇鹏, 徐敏, 孙志浩. 琥珀酸放线杆菌发酵培养基的优化. 工业微生物[J]. 2007, 37(5): 1-5, http://lib.cqvip.com/Qikan/Article/Detail?id=25830133.
[43] 朱蕾蕾, 刘宇鹏, 郑璞, 孙志浩. 一株琥珀酸产生菌的筛选及鉴定. 微生物学通报[J]. 2007, 34(1): 80-84, http://lib.cqvip.com/Qikan/Article/Detail?id=23837272.
[44] 赵丽青, 朱蕾蕾, 孙志浩, 郑璞. 转化异丁香酚生成香草醛纺锤芽孢杆菌的筛选. 微生物学通报[J]. 2006, 33(1): 72-77, http://lib.cqvip.com/Qikan/Article/Detail?id=21207179.
发表著作
Chapter 3: Channel protein FhuA as a promising biomolecular scaffold for bioconjugates, Bio-Synthetic Hybrid Materials and Bionanoparticles: A Biological Chemical Approach Towards Material Science, Royal Society of Chemistry, 2015-09, 第 1 作者

科研活动

   
科研项目
( 1 ) 中科院****, 主持, 研究所(学校), 2016-01--2018-12
( 2 ) 研究组启动经费, 主持, 市地级, 2016-06--2018-06
参与会议
(1)Directed evolution of arginine deiminase for anti-­tumor application   中德“生物基化学品暨生物炼制”双边研讨会   Leilei Zhu   2015-10-06
(2)Channle protein FhuA: a versatile biomolecular scaffold for biohybrid systems   Leilei Zhu   2015-03-05
(3)Protein engineering of enzymes for improving ionic liquid resistance   中德“生物基化学品暨生物炼制”双边研讨会   Leilei Zhu   2014-10-07