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马明

研究员、博士生导师

马明 博士 研究员

Ming Ma, Ph. D., Assistant Professor (PI)

 

电子邮箱E-mail:  mma@bjmu.edu.cn

实验室网站Group websitehttp://sklnbd.bjmu.edu.cn/k/e/action/ListInfo/?classid=256

 

教育背景

2003--2006博士,药物化学,中国医学科学院北京协和医学院药物研究所

2000--2003硕士,药物化学,山东中医药大学中药学院

1996--2000学士,中药学,山东中医药大学  

 

工作经历

2016.1--现在,入选北京大学“优秀青年人才计划”(研究员),博士生导师,北京大学药学院bet356官网为什么上不去_bet356娱乐场注册送19_bet356注册身份证认证

2011.5--2016.1博士后,美国斯克里普斯(SCRIPPS FLORIDA)研究所化学系

2006.7--2011.4助理研究员,中国科学院生物物理研究所生物大分子国家重点实验室

 

 

Education 

2003--2006,  Ph. D., pharmaceutical chemistry, institute of materiamedica, Chinese academy of medical sciences & Peking union medical college.  

2000--2003,  M. S., pharmaceutical chemistry, academy of traditional Chinese medicine, Shandong university of traditional Chinese medicine.

1996--2000,  B. S., traditional Chinese medicine, academy of traditional Chinese medicine, Shandong university of traditional Chinese medicine.

  

Research Experiences

2016.1--    ,  assistant professor (PI, The Recruitment Program of Youth Experts), department of natural medicines, school of pharmaceutical sciences, Peking university.

2011.5--2016.1,  research associate, department of chemistry, The Scripps Research Institute (Florida).

2006.7--2011.4,  assistant professor, institute of biophysics, Chinese academy of sciences.

 

 

研究方向

微生物来源的天然产物为人类健康作出了巨大贡献。1945年和1952年的诺贝尔医学与生理学奖分别颁给了青霉素(penicillin)和链霉素(streptomycin)的发现,而在60多年后的2015年,诺贝尔医学与生理学奖又颁给了阿维霉素(avermectin)和青蒿素(artemisinin)的发现。在这四个获奖天然产物里除了青蒿素外其余三个均来源于微生物。而在微生物里面,放线菌又是天然药物的重要来源,比如抗癌药物放线菌素(dactinomycin)和博来霉素(bleomycin)、抗菌药物万古霉素(vancomycin)和达托霉素(daptomycin)都是放线菌中发现的、未经过化学修饰直接成药的天然产物。 

我们的科学研究聚焦在放线菌中结构复杂或生物活性特异的天然产物的生物合成。我们将运用微生物学、分子生物学、生物化学、结构生物学、生物信息学以及天然产物化学多学科交叉的技术方法,阐明放线菌基因组DNA中哪些基因负责天然产物的生物合成、这些基因编码的蛋白质在生物合成中催化何种反应以及如何催化这些反应、生物体是如何使这些酶促反应按照严格的次序进行下去的、如何人工改造生物合成途径使生物体产生结构更复杂或生物活性更特异的天然产物类似物等等。相关研究内容可简述为以下五个方面:

(1)对天然产物生物合成基因进行敲除,通过对突变体化学表型进行分析,考察基因敲除对生物合成途径的影响,进而推测基因的功能。

(2)对生物合成基因进行异源表达,对编码蛋白质进行纯化,构建体外酶活表征体系以验证基因的功能并揭示酶催化反应中对底物的位置和立体选择性。

(3)对生物合成基因编码蛋白质进行晶体结构研究,尤其侧重蛋白质-蛋白质或蛋白质-底物复合物晶体结构研究,进而阐释酶催化反应的具体机制。 

(4)在阐明生物合成途径的基础上,对生物合成途径进行人工改造或组合生物合成研究,以产生结构更复杂或生物活性更特异的天然产物类似物。  

(5)在已有的各类天然产物生物合成机制的阐明基础上,运用基因组挖掘技术对新颖的天然产物进行探索发现。  

通过以上各项研究,我们拟发现天然产物生物合成研究中新的化学和生物学现象,为天然产物研究的整体发展作出贡献。

 

 

 

发表论文(2016年之前)publications before 2016    

 

18.   Ming Ma#, Jeremy R. Lohman#, Tao Liu#, Ben Shen*. C-S bond cleavage by a polyketide synthase domain. Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 10359-10364.     

 

17.   Sheng-Xiong Huang#, Bong-Sik Yun#, Ming Ma#, Hirak S. Basu, Dawn R. Church, Gudrun Ingenhorst, Yong Huang, Dong Yang, Jeremy R. Lohman, Gong-Li Tang, JianhuaJu, Tao Liu, George Wilding, Ben Shen*. Leinamycin E1 acting as an anticancer prodrug activated by reactive oxygen species. Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 8278-8283.    

 

16.   Ming Ma, Mostafa E. Rateb, QihuiTeng, Dong Yang, Jeffrey D. Rudolf, Xiangcheng Zhu, Yong Huang, Li-Xing Zhao, Yi Jiang, Xiuling Li, Christoph Rader, YanwenDuan, Ben Shen*. Angucyclines and angucyclinones from Streptomyces sp. CB01913 featuring C-ring cleavage and expansion. J. Nat. Prod., 2015, 78, 2471-2480.    

 

15.   Jeremy R. Lohman, Ming Ma, Jerzy Osipiuk, BoguslawNocek, Youngchang Kim, Chang Changsoo, Marianne Cuff, Jamey Mack, Lance Bigelow, Hui Li, Mike Endres, GyorgyBabnigg, AndrzejJoachimiak, George N. Phillips, Jr., Ben Shen*. Structural and evolutionary relationships of “AT-less” polyketide synthase ketosynthases. Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 12693-12698.          

 

14.  XiangweiGao, Ji Wan, Botao Liu, Ming Ma, Ben Shen, Shu-Bing Qian*. Quantitative profiling of initiating ribosomes in vivo. Nat. Methods, 2015, 12, 147-153.     

 

13.  Tao Liu, Ming Ma, Hui-Ming Ge, Chunying Yang, John Cleveland, Ben Shen*. Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin. Bioorg. Med. Chem. Lett., 2015, 25, 4899-4902.          

 

12.  Jeffrey D. Rudolf, Lance Bigelow, Changsoo Chang, Marianne E. Cuff, Jeremy R. Lohman, Chin-Yuan Chang, Ming Ma, Dong Yang, Shonda Clancy, GyorgyBabnigg, AndrzejJoachimiak, George N. Phillips, Jr., Ben Shen*. Crystal structure of the zorbamycin-binding protein ZbmA, the primary self-resistance element in Streptomyces flavoviridis ATCC 21892. Biochemistry, 2015, 54, 6842-6851.      

 

11.   Zhilong Yang, Shuai Cao, Craig A. Martens, ZhiXie, Ming Ma, Ben Shen, Bernard Moss*. Deciphering poxvirus gene expression by RNA sequencing and ribosome profiling. J. Virol., 2015, 89, 6874-6886.        

 

10.  Jeong-Woo Seo#, Ming Ma#, Thomas Kong#, JianhuaJu, Si-Kyu Lim, Hui Jiang, Jeremy R. Lohman, Emmanuel Zazopoulos, Chris M. Farnet, Ben Shen*. Comparative characterization of the lactimidomycin and iso-migrastatin biosynthetic machineries revealing unusual features for acyltransferase-less type I polyketide synthases and providing an opportunity to engineer new analogues. Biochemistry, 2014, 53, 7854-7865.    

 

9.    PengfeiXie#, Ming Ma#, MostafaRateb, KhaledShaaban, Zhiguo Yu, Shengxiong Huang, Jeremy Lohman, Dong Yang, Jeffrey Rudolf, Ben Shen*. Biosynthetic potential-based strain prioritization for natural product discovery – a showcase for diterpenoid producing actinomycetes. J. Nat. Prod., 2014, 77, 377-387.         

 

8.     Jeremy R. Lohman, Ming Ma, Marianne Cuff, Lance Bigelow, Jessica Bearden, GyorgyBabnigg, AndrzejJoachimiak, George Phillips, Ben Shen*. The crystal structure of BlmI as a model for nonribosomal peptide synthetasepeptidyl carrier proteins. Proteins, 2014, 82, 1210-1218.        

 

7.    Min Yin, Yijun Yan, Jeremy R. Lohman, Sheng-xiong Huang, Ming Ma, Guang-rong Zhao, Li-huaXu, Wensheng Xiang, Ben Shen*. Cycloheximide and actiphenol production in Streptomyces sp. YIM56141 governed by single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase. Org. Lett., 2014, 16, 3072-3075.        

 

6.    Alexander Koch, DariaGawron, Sandra Steyaert, Elvis Ndah, JeroenCrappe, Sarah De Keulenaer, Ellen De Meester, Ming Ma, Ben Shen, Kris Gevaert, Wim Van Criekinge, Petra Van Damme, GerbenMenschaert*. A proteogenomics approach integrating proteomics and ribosome profiling increases the efficiency of protein identification and enables the discovery of alternative translation start sites. Proteomics, 2014, 14, 2688-2698.     

 

5.     Ming Ma#, Thomas Kwong#, Si-kyu Lim, JianhuaJu, Jeremy R. Lohman, Ben Shen*.  Post-polyketide synthase steps in iso-migrastatin biosynthesis, featuring tailoring  enzymes with broad substrate specificity. J. Am. Chem. Soc., 2013, 135, 2489-2492. 

 

4.   Noam Stern-Ginossar, Ben Weisburd, Annette Michalski, Vu ThuyKhanh Le, Marco Y. Hein, Sheng-Xiong Huang,  Ming Ma, Ben Shen, Shu-Bing Qian, HartmutHengel, Matthias Mann, Nicholas T. Ingolia, Jonathan S. Weissman*. Decoding human cytomegalovirus. Science, 2012, 338, 1088-1093.     

 

3.   Ming Ma#, Stephen G. Bell#, Wen Yang, YimingHao, Nicholas H. Rees, Mark Bartlam, Weihong Zhou, Luet-Lok Wong and ZiheRao*. Structural analysis of CYP101C1 from Novosphingobiumaromaticivorans DSM12444. ChemBioChem, 2011, 12, 88-99.        

 

2.    Ming Ma, Jielu Zhao, Sujuan Wang, Shuai Li, Yongchun Yang, Jiangong Shi*, Fan Xiao and Lan He. Bromophenols coupled with nucleoside bases and brominated tetrahydroisoquinolines from the red alga Rhodomelaconfervoides. J. Nat. Prod., 2007, 70, 337-341.

 

1.    Ming Ma, Jielu Zhao, Sujuan Wang, Shuai Li, Yongchun Yang, Jiangong Shi*, and Lan He. Bromophenols coupled with methyl gamma-ureidobutyrate and bromophenol sulfates from the red alga Rhodomelaconfervoides. J. Nat. Prod., 2006, 69, 206-210.