张立新
发布人:生工学院网站管理员  发布时间:2016-10-19   动态浏览次数:1505

 

张立新

生物工程专业:博士生导师/硕士生导师

生物工程领域:工程硕士生导师

 

   

    张立新研究员2004年回国以来在微生物化学生物学领域做出了系统性和开创性的研究:利用自主构建的我国南海微生物天然产物资源库高通量筛选活性化合物,研究其作用机制与生物合成机制并提高产量。揭示了库中青蒿素类的新环内过氧桥键合酶的功能和机制。同时针对库中一些有望开发成为具有自主知识产权的抗真菌药物,揭示了其克服抗真菌药物毒副作用和耐药性的新机制。还通过专利转化,使得我国成为世界上阿维菌素(具有抗真菌和抗细菌耐药性的新机制)的唯一生产国。

1)在基础及应用基础研究方面:已在Nature等杂志上发表200篇论文,主编或参编写八部学术专著(英文四部),他引超过三千次,h-index: 30。作为国家杰出青年基金终评优秀和2014年“英国皇家化学会-罗氏青年科学家奖”(Royal Society of Chemistry-Roche Young Investigator Award)获得者、“新世纪百千万人才工程”国家级人选及中国科学院“百人计划”终评优秀获得者,他还担任康奈尔大学、哈佛大学客座教授,曼彻斯特大学的科学顾问(Advisor)和海外评审专家及美国,欧盟和英国自然科学基金的评审委员;并担任《Synthetic and Systems Biotechnology》主编、《Applied Microbiology and Biotechnology》副主编,曾被邀请在第十二届国际工业微生物遗传学会(GIM)年会上做主题报告;将在第十八届国际放线菌学会(ISBA)年会上做主旨报告;多次应邀参加国际会议并作特邀报告。

2)在成果转化方面:张立新获得多项国内国际专利发明授权和转让,“阿维菌素的微生物高效合成及其生物制造”荣获2016年度国家科技进步二等奖(第一完成人);“绿色生物农药阿维菌素高产菌改造及其产业化研究”获内蒙古自治区 2011年度科技进步一等奖(第一完成人),使得我国的阿维菌素(2015年诺贝尔生理医学奖)产业打破美国默克公司的技术垄断,从无到有,从弱到强,再到完全独占国际市场并解决了核心菌株自主知识产权、产品安全、环保以及高效发酵的系统工艺,完成了一个自主创新、弯道超车的壮举。

3)在团队合作、引领学科发展方面:张立新研究员作为973项目首席科学家,促使15名队友更加优秀,成果累累。张立新作为通讯作者联合英美日加四个国家的5名教授编著的电子书影响很大,网上阅览113,431(view)。他曾作为会议共同主席,举办了3个国际会议和1次“香山会议”。他被选为2016-2017年国际化学生物学会(ICBS)主席、2015-2016年实验室自动化与筛选协会(SLAS)亚洲委员会主席,国际放线菌学会(ISBA)董事等,为我国微生物科学的发展做出了卓越的贡献。


电话:021-64252575 email: lxzhang@ecust.edu.cnlzhang03@gmail.com

URL   http://zhanglab.caspmi.cn/


代表性论文

1.Wang Minxuan, Carver Jeremy J, Shi Wenyuan, Liu Xueting, Zhang Lixin, Knight Rob, Moore Bradley S, Dorrestein Pieter C*, Bandeira Nuno*, et al. 2016. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nature Biotechnology. 34(8):828-837. doi: 10.1038/nbt.3597. IF=43.113

2.Yan Wupeng, Song Heng, Song Fuhang, Guo Yisong, Wu Cheng-Hsuan, Sae Her Ampon, Pu Yi, Wang Shu, Naowarojna Nathchar, Weitz Andrew, Hendrich Michael P., Costello Catherine E., Zhang Lixin*, Liu Pinghua*, Jessie Zhang Yan*. 2015. Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme. Nature 527, 539–543.IF=41.296

3.Wang Qian, Song Fuhang, Xiao Xue, Huang Pei, Li Li, Aaron Monte, Wael M. Abdel-Mageed, Wang Jian, Guo Hui, He Wenni, Xie Feng, Dai Huanqin, Liu Miaomiao, Chen Caixia, Xu Hao, Liu Mei, Andrew M. Piggott, Liu Xueting*, Robert J. Capon*, Zhang Lixin*. Abyssomicins from the South China Sea deep-sea sediment Verrucosispora sp.: Natural thioether Michael addition adducts as antitubercular prodrugs. Angew. Chem.-Int. Edit. 2013, 52, 1231-1234. (IF13.560)

4.Kyrpides Nikos C*, Hugenholtz P, Eisen JA, Woyke T, Göker M, Parker CT, Amann R, Beck BJ Zhang Lixin, Klenk Hans-Peter*, et al. (2014) Genomic encyclopedia of bacteria and archaea: sequencing a myriad of type strains. PLoS biology 12(8):e1001920. IF=12.807

5.Zhang Lixin, J. Chen and H. Fu*. 1999. Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. Proc Natl Acad Sci USA. 96 (15): 8511-8515. IF=10.783

6.Bai Chaoxian# ,Zhang Yang# , Zhao Xuejin# , Hu Yiling, Xiang Sihai, Miao Jin, Lou Chunbo*, Zhang Lixin*. (2015) Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces. Proc Natl Acad Sci USA. 112 (39), 12181-6.IF=10.563

7.Joseph Scott Zarins-Tutt, Tania Triscari Barberi, Hong Gao, Andrew Mearns-Spragg, Lixin Zhang, David J. Newmand, Rebecca Jane Miriam Goss*. Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products. Nat Prod Rep. 2016, 33(1):54-72.IF=10.107

8.Ashforth Elizabeth Jane, Fu Chengzhang, Liu Xiangyang, Dai Huanqin, Song Fuhang, Guo Hui, Zhang Lixin*.  Bioprospecting for antituberculosis leads from microbial metabolites. Nat Prod Rep. 2010,27, 1709-1719. (IF9.8)

9.Jing Zhao , Yuhong Du, John R. Horton, Anup K. Upadhyay, Bin Lou, Yan Bai, Xing Zhang, Lupei Du, Minyong Li, Binghe Wang, Lixin Zhang, Joseph T. Barbieri, Fadlo R. Khuri, Xiaodong Cheng, Haian Fu, et al. 2011. Discovery and structural characterization of FOBISIN 101 as a small molecule 14-3-3 protein-protein interaction inhibitor. Proc Natl. Acad. Sci. USA. 108(39): 16212-6. IF=9.771

10.Zhang Lixin*, Yan K, Zhang Y, Huang R, Bian J, Zheng C, Sun H, Chen Z, Sun N, et al. High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proc Natl Acad Sci U S A, 2007, 104(11), 4606-4611. (IF=9.598)

11.Zhuo Ying, Zhang Wenquan, Chen Difei, Gao Hong, Tao Jun, Liu Mei, Gou Zhongxuan, Zhou Xianlong, Ye Bangce, Zhang Qing, Zhang Siliang, Zhang Lixin*. Reversebiological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitili., Proc. Natl. Acad. Sci. U S A, 2010,107(25), 11250-11254. (IF9.38)

12.Zhang Lixin, H. Wang, D. Liu, R. Liddington, H. Fu*. 1997. Raf-1 kinase and Exoenzyme S interact with 14-3-3 through a common site involving lysine-49. J Biol Chem. 272: 13717-13724.IF=8.765

13.Liu J, Chen Y, Wang W, Ren M, Wu P, Wang Y, Li C, Zhang Lixin, Wu H, Weaver DT, Zhang B. 2016. Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraeaMetab Eng. 2016, S1096-7176 (16) 30186-0. IF=8.328

14.Zhang Lixin*, An Rong, Wang Jinping, Sun Nuo, Zhang Si, Hu Jiangchun, Kuai Jun. Exploring novel bioactive compounds from marine microbes. Curr. Opin. Microbiol. 2005, 8(3), 276-281. (IF=7.654)

15.Zhang Lixin, H. Wang, B. Wang, J. Barbieri, H. Fu*. 1999. Residues in the conserved amphipathic groove of 14-3-3 required for activation of Exoenzyme S of Pseudomonas aeruginosa. Biochemistry 38: 12159-12164.IF=7.366

16.Song Fuhang, Liu Xinru, Guo Hui, Ren Biao, Chen Caixia, Andrew M. Piggott, Yu Ke, Gao Hong, Wang Qian, Liu Mei, Dai Huanqin, Zhang Lixin*, Robert J. Capon. Brevianamides with antitubercular potential from a marine-derived isolate of Aspergillus versicolor. Org. Lett. 2012, 14 (18), 4770–4773. (IF=5.862)

17.Abdel-Mageed Wael M*, Bayoumi Soad A L, Al-Wahaibi Lamya H, Li Li, Sayed Hanaa M, Abdelkader Mohamed S A, El-Gamal Ali A, Liu Mei, Zhang Jingyu, Zhang Lixin*, Liu Xueting*. 2016. Noncyanogenic Cyanoglucoside Cyclooxygenase Inhibitors from Simmondsia chinensis, Org Lett 18, 1728-1731. IF=5.849

18.Wang Fen, Wang Yanjie, Ji Junjie, Zhou Zhan, Yu Jingkai, Zhu Hua, Su Zhiguo, Zhang Lixin*, Zheng Jianting*. Structural and Functional Analysis of the Loading Acyltransferase from Avermectin Modular Polyketide Synthase. ACS Chem Biol. 2015, 10(4), 1017–1025. (IF=5.648)

19.Zhang Huifang M, Dai Huanqin, Hanson Paul J, Li Huidong, Guo Hui, Ye Xin, Hemida Maged G, Wang Luoqiang, Tong Yaojun, Qiu Ye, Liu Selina, Wang Fengping, Song Fuhang, Zhang Buchang, Wang Jianguo*, Zhang Lixin*, Yang Decheng*. Antiviral Activity of an Isatin Derivative via Induction of PERK-Nrf2-mediated suppression of Cap-independent Translation. ACS Chem. Biol. 2014, 9 (4), 1015–1024. (IF=5.648)

20.Zhang Jingyu, Abdel-mageedWael M., Liu Miaomiao, Huang Pei, He Wenni, Li Li, Song Fuhang, Dai Huanqin, Liu Xueting*, Liang Jingyu*, Zhang Lixin*. Caesanines A-D. New cassanediterpenes with unprecedented N bridge from Caesalpiniasappan. Org. Lett. 2013, 15(18), 4726-4729. (IF5.563)

21.Chen Caixia, Liu Xueting, Abdel-Mageed Wael M, Guo Hui, Hou Weiyuan, Jaspars Marcel, Li Li, Xie Feng, Ren Biao, Wang Qian, Dai Huanqin, Song Fuhang*, Zhang Lixin*. Nivetetracyclates A and B: novel compounds isolated from Streptomyces niveusOrganic Letters. 2013,15(22), 5762-5765. (IF5.563)

22.Wang Fen, Wang Yanjie, Li Junjie, Zhou Zhan, Yu Jingkai, Zhu Hua, Su Zhiguo, Zhang Lixin*, Zheng Jianting*. (2015) Structural and Functional Analysis of the Loading Acyltransferase from Avermectin Modular Polyketide Synthase. ACS Chem Biol. 10(4):1017-1025.IF=5.459

23.Li Wenru, Shi Qingshan*, Dai Huanqin, Liang Qing, Xie Xiaobao, Huang Xiaomo, Zhao Guangze, Zhang Lixin*. (2016). Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicansScientific Reports, Mar 7;6:22805. doi: 10.1038/srep22805. IF=5.228

24.Wen-Ru Li, Qingshan Shi, Huan-Qin Dai, Qing Liang, Xiao-Bao Xie, Xiao-Mo Huang, Guang-Ze Zhao, Zhang Lixin*. (2016). Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans.Scientific Reports, 2016, 7; 6:22805. IF=5.228

25.Tong Yaojun, Charusanti Pep, Zhang Lixin , Weber Tilmann* , Lee Sang Yup*. (2015) CRISPR-Cas9 based engineering of actinomycetal genomes. ACS Synthetic Biology. 4 (9), 1020–1029.IF=5.037

26.Chen Xing , Ren Biao , Chen Ming , Wang Quanxin , Zhang Lixin*, and Yan Guiying*. NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning, PLoS Comput. Biol.2016, 12(7): e1004975. IF=5.017

27.Danielle M. Williams, Heath Ecroyd, Katy L. Goodwin, Huanqin Dai, Haian Fu, Joanne M. Woodcock, Zhang Lixin *, John A. Carver*. 2011. NMR spectroscopy of 14-3-3 reveals a flexible C-terminal extension: differentiation of the chaperone and phosphoserine binding activities of 14-3-3. Biochem. J. 437(3):493-503. IF=5.016


代表性授权专利

1.张立新,孙诺。小檗碱及其结构类似物在逆转多药耐药泵中的应用,ZL 2008 1 0112350.1  (授权公告日:2010922日)

2.朱宝利,胡永飞,张立新。一种酯酶及其编码基因与应用。授权号:ZL 200810222671.7 (授权公告日:20101215日)

3.张立新,刘梅,高弘,周贤龙,徐兵,刘金涛,卓英,陈涤非,一种制备阿维菌素的方法及其专用菌株。授权号:ZL 200810227639.8 (授权公告日:201098日)

4.张立新,宋福行,任彪,代焕琴,郭徽,童垚俊,傅成章。聚酮化合物及其制备方法与应用。授权号:ZL 201010034356.9 (授权公告日:201288日)

5.张立新,宋福行,郭徽,代焕琴,任彪,童垚俊,傅成章。聚酮类化合物及其制备方法与应用。授权号:ZL201010034355.4  授权公告日:201288日)

6.张立新,宋福行,陈彩霞,王倩,郭徽,傅成章,代焕琴,刘雪婷,谢峰,杨娜,余珂。一株链霉菌及其在生产棘霉素中的应用。授权号:ZL 201110366624.1 (授权公告日:20121219

7.张立新,宋福行,陈彩霞,郭徽,傅成章,代焕琴,刘雪婷,谢峰,杨娜,余珂,王倩。一株链霉菌及其在生产放线菌素中的应用。授权号:ZL201110366034.9 (授权公告日:2013116日)

8.张立新,傅成章,谢峰,郭徽,代焕琴. 一种碱性酯酶及其编码基因与应用。授权号:ZL 201010543915.9  (授权公告日:2013710日授权)

9.张立新,宋福行,陈彩霞,郭徽,代焕琴,谢峰,任彪。抗肿瘤化合物及其制备方法与应用。授权号:ZL 201110185704.7  (授权公告日:201394日)

10.张立新,宋福行,陈彩霞,任彪,刘雪婷,代焕琴,郭徽,杨娜。一种抗真菌的药物组合物。授权号:ZL201210245954.X (授权公告日:20131023日)

11.张立新,张涛,刘金涛,贾晓鹏。白僵菌素合成相关蛋白质系统及其编码基因簇与应用。授权号:ZL201110322036.8 (授权公告日:2014528日)

12.张立新,卓英,刘梅,高弘,周贤龙。一种生产阿维菌素的基因工程方法及其专用菌株。授权号:ZL201010173186.2 (授权公告日:2014528日)(授权公告日:2014528日)

13.张立新,代焕琴,宋福行,王倩,王剑,刘向阳,任彪. 具有抗肿瘤活性的螺内酰胺生物碱化合物及其制备方法和应用。授权号:ZL201010221389.4 (授权公告日:2014528日)

14.张立新,互动药物的筛选。授权号:ZL200480034073.7 (授权公告日:2014514日)

15.张立新,宋福行,郭徽,代焕琴,陈彩霞,杨娜,童垚俊,余珂。一株链霉菌及其在生产具有抗菌作用的化合物中的应用。授权号:ZL201310069479.X (授权公告日:2014917日)

16.张立新,刘雪婷,亚伦蒙蒂,尼古拉斯齐特默,蓝苑元威廉斯沃恩, 汤姆沃克,代焕琴,陈彩霞。抗多种耐药菌化合物及其制备方法与应用。授权号:ZL201110436175.3 (授权公告日:201425日)

17.张立新,宋福行,陈彩霞,郭徽,刘雪婷,代焕琴。抗肿瘤化合物及其制备方法与应用。授权号:ZL201210067370.8 (授权公告日:201464日)

18.王建国,张立新,李在顺,郭徽,王伟民,代焕琴,李正民,宋福行。吲哚满二酮缩氨基硫脲类化合物及其抗耐药菌用途,授权号:ZL201310481973.7 (授权公告日:2015422日)

19.张立新,梁敬钰,张敬宇,刘雪婷,刘苗苗. 一种抗菌化合物及其制备方法与应用。专利号ZL201310378741.99(授权公告日:2015527

20.张立新,刘雪婷,王倩,宋福行,陈彩霞,王剑,郭徽,代焕琴,黄佩。来源于海洋疣孢菌的多环聚酮类化合物及其制备方法与应用。专利号:201210079317.X  (授权公告日:2015617

21.张立新,白超弦,刘梅,任彪。一种抗真菌的药物组合物。专利号:ZL201310478768.5(授权公告日:2015729

22.王建国,张立新,商建丽,任彪,王伟民,郭徽,李正名,代焕琴。苯次磺酰胺衍生物及其在制备抗菌药物中的用途. 专利号:ZL 201110440557.3 (授权公告日:2015812日)

23.张立新,刘梅,宋福行,代焕琴,高弘,刘向阳,任彪。一种高通量筛选生物表面活性剂的方法。专利号:ZL 201310255022.8  (授权公告日:20151028日)

24.张立新,宋福行,郭徽,代焕琴,陈彩霞,杨娜,童垚俊,余珂。一种化合物及其在制备抗菌药物中的应用。专利号:ZL201310069411.1 (授权公告日:201616日)

25.张立新,何文妮,刘雪婷等。一种真菌转化的抗菌活性物质及其制备方法与应用。专利号:ZL20151016433. (授权公告日:201697日)


代表性科研项目

1.从海洋疣孢菌属中勘探和挖掘抗结核分枝杆菌活性的小分,国家自然基金重点项目,31430002297万元,2015/01-2019/12,主持

2.针对病原菌与宿主互做关系筛选获得克服耐药菌的新型抗生素,国家自然基金委国际合作重大项目,31320103911, 263万元,2014/01-2018/12,主持

3.合成微生物体系的适配性研究973计划,2013CB734004694万元,2013/01-2017/12,主持

4.欧盟第七框架计划“PharmaSea”项目,Increasing Value and Flow in the Marine Bio-discovery Pipeline2012/10-2016/0914.85万欧元,主持

5.微生物活性物质抗耐药真菌的机制研究,国家自然基金委国家杰青基金项目,31125002 2012/01-2015/12240万元,主持

6.互动抗真菌药物白僵菌素的临床前研究,重大新药创制课题,2011ZX09102-011-11367.24万元,2011/01-2014/12,主持

7.结核病新药发现计划,比尔盖茨基金会和全球结核病药物(TB Drug)研发联盟项目,2009/05-2011/05260万元,主持

8.海洋放线菌:多样性及在天然药物和清洁工业生物催化剂中的研究,国家科技部国际科技合作重大项目,2007DFB31620264万元,2008/01-2011/01,主持

9.海洋微生物及其代谢产物库的高通量筛选研究,中科院百人计划项目,173万元,2006/05-2009/05,主持