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Youming Zhang
Phone number: 0086-531-88363082
Fax number: 
E-mail: zhangyouming@sdu.edu.cn
Title: Professor

EDUCATION

Ph.D: 1990.5.-1994.12., Ruprecht-Karls-Universität Heidelberg, Molecular Biology and Cell Biology

Master: 1985.9.-1988.7., Chinese Academy of Medical Sciences & Peking Union Medical College, Biochemistry and Molecular Biology

Bachelor: 1981.9.-1985.7., Xiamen University, Biochemistry

WORK EXPERIENCE

2013.4.-Present, Shandong University, Professor; Director of the State Key Laboratory of Microbial Technology; Winner of “One Thousand Talents Program” (The Recruitment Program of Global Experts) in China in 2014

2000.7.-2013.2., Gene Bridges GmbH, Germany, Chief Scientific Officer and Founder

1998.7.-2000.6., European Molecular Biology Laboratory (EMBL), Germany, Long-term fellowship of European Molecular Biology Organization (EMBO)

1997.1.-1998.6., European Molecular Biology Laboratory (EMBL), Germany, Postdoctoral researcher

1995.1.-1996.12. Ruprecht-Karls-Universität Heidelberg, Postdoctoral researcher

1988.9.-1990.4., Chinese Academy of Medical Sciences & Peking Union Medical College, research assistant

RESEARCH INTERESTS

1. Establishment and development of DNA recombineering technology platform: As an innovator of Red/ET recombineering and DNA direct cloning technologies which have been applied in advanced DNA engineering laboratories and many biotechnology and pharmaceutical companies all over the world, Prof. Zhang’s outstanding achievements were published in Nature, Nature Biotechnology, Nature Nanotechnology and other leading journals and made him become a leading scientist in the field of DNA recombineering. He will lead his group to make new contributions in the development of DNA recombineering system, mechanism elucidation of this system and exploitation of its application.

2. Investigation of bioactive natural products using DNA recombineering system: Using this system, Prof. Zhang and his cooperators made deep insights into the production and structurally modification of many valuable natural products (such as antitumor and antibacterial compounds) as well the biosynthesis of magnetic nanostructures in a foreign organism by transfer of bacterial magnetosome gene transfer (published in Nat Nanotechnol). His group will apply this system into the studies on more bioactive natural products with anti-tumor, anti-microbial, anti-aging and/or anti-cholesterol bioactivity, focusing on the new pathway discovery, structural modification and biosynthesis of these potential drugs.

3. Establishment of humanized animal models using DNA recombineering system:Prof. Zhang’s group will apply their own-developed site-specific recombination technology (seamless mutagenesis by recombineering using ccdB for counterselection, published in Nucleic Acids Res), recombineering technology for mouse targeting and newly developed CRISPR/Cas9 technology into the construction of humanized animal models, hoping to produce humanized antibodies and to produce humanized animals for drug evaluation.

4. Targeting tumors and inhibiting of tumor growth by bacterial strains: some bacterial strains, like E. coli, can colonize in tumors but not other organs. Prof. Zhang’s group discovered and isolated a few bacterial strains which already produce strong anticancer drugs and also can colonize in tumors. By collaborating with Prof. Rolf Müller in Germany, they can clone, engineer and transfer the most active anticancer drug producing gene clusters into these tumor colonization bacteria strains and thus make them engineered killers delivering their load (anticancer drug) to the tumor cells.

RESEARCH PROGRAMS

1. 2016/01−2020/12, Base for Microbial Genome Engineering Innovation and Talent Recruitment, the Ministry of Education and State Bureau of Foreign Experts Affairs

2. 2017 /01-2020 /12, Engineering of biosynthetic pathways of proteasome inhibitor syrbactins to generate new antitumor compounds utilizing RED/ET DNA recombineering,National Natural Science Foundation of China

3. 2009-2012, Lipopeptide and secondary metabolites pathway expression with recombineering in Burkholderia und Bacillus, Federal Ministry of Education and Research, Germany

SELECTED PUBLICATIONS

1. Hu S, Liu Z, Zhang X, Zhang G, Xie Y, Ding X, Mo X, Stewart AF, Fu J*, Zhang Y*, Xia L*. "Cre/loxP plus BAC": a strategy for direct cloning of large DNA fragment and its applications in Photorhabdus luminescens and Agrobacterium tumefaciens. Sci Rep. 2016 Jul 1;6:29087.

2. Wang H, Li Z, Jia R, Hou Y, Yin J, Bian X, Li A, Müller R, Stewart A F, Fu J*, Zhang Y*. RecET direct cloning and Redαβ recombineering of biosynthetic gene clusters, large operons or single genes for heterologous expression. Nature Protocols, 2016/6,11:1175-79

3. Tu Q, Herrmann J, Hu S, Raju R, Bian X, Zhang Y*, Müller R*. Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering. Sci Rep. 2016 Feb 15;6:21066.

4. Yin J, Hoffmann M, Bian X, Tu Q, Yan F, Xia L, Ding X, Stewart AF, Müller R*, Fu J*, Zhang Y*.Direct cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2). Sci Rep. 2015 Oct 13;5:15081.

5. Tang B, Yu Y, Zhang Y*, Zhao G*, Ding X*. Complete genome sequence of the glidobactin producing strain [Polyangium] brachysporum DSM 7029. J Biotechnol. 2015 Sep 20;210:83-84.

6. Bian X, Plaza A, Yan F, Zhang Y*, Müller R*. Rational and efficient site-directed mutagenesis of adenylation domain alters relative yields of luminmide derivatives in vivo. Biotechnol Bioeng. 2015 Jul;112(7):1343-53.

7. Tang Y, Frewert S, Harmrolfs K, Herrmann J, Karmann L, Kazmaier U, Xia L, Zhang Y*, Muller R*. Heterologous expression of an orphan NRPS gene cluster from Paenibacillus larvae in Escherichia coli revealed production of sevadicin. J Biotechnol. 2015 Jan; 20;194:112-4.

8. Yin J, Zhu H, Xia L, Ding X, Hoffmann T, Hoffmann M, Bian X, Müller R, Fu J, Stewart F, and Zhang Y*. A new recombineering system for Photorhabdus and Xenorhabdus. Nucleic Acids Res. 2015 Mar 31;43(6):e3.

9. Bian X, Plaza A, Zhang Y*, Müller R*. Two more pieces of the colibactin genotoxin puzzle from Escherichia coli show incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety. Chem Sci. 2015, 6(5): 3154−60.

10. Bian X, Huang F, Wang H, Klefisch T, Müller R* and Zhang Y*. Heterologous production of glidobactins/luminmycins in Escherichia coli nissle containing the glidobactin biosynthetic gene cluster from burkholderia DSM7029. ChembioChem. 2014 Oct 13;15(15):2221-4.

11. Bian X, Huang F, Wang H, Klefisch T, Müller R* & Zhang Y*. Heterologous production of glidobactins/luminmycins in Escherichia coli Nissle containing the glidobactin biosynthetic gene cluster from Burkholderia DSM7029. Chembiochem. 2014, doi: 10.1002/cbic.201402199 (SCI, 5-year IF: 3.3).

12. Kolinko I, Lohße A, Borg S, Raschdorf O, Jogler C, Tu Q, Pósfai M, Tompa E, Plitzko JM, Brachmann A, Wanner G, Müller R, Zhang Y* & Schüler D*. Biosynthesis of magnetic nanostructures in a foreign organism by transfer of bacterial magnetosome gene transfer. Nat Nanotechnol. 2014, 9(3):193-197 (SCI, 5-year IF: 38.6).

13. Wang H, Bian X, Xia L, Ding X, Müller R, Zhang Y*, Fu J* & Stewart AF*. Improved seamless mutagenesis by recombineering using ccdB for counterselection. Nucleic Acids Res. 2013, 42(5):e37(SCI, 5-year IF: 8.4, 2013 IF: 8.8).

14. Hu S, Fu J, Huang F, Ding X, Stewart AF, Xia L*, & Zhang Y*. Genome engineering of Agrobacterium tumefaciens using the lambda Red recombination system. Appl Microbiol Biotechnol. 2014, 98(5):2165-2172 (SCI, 5-year IF: 3.8).

15. Ongley SE, Bian X, Zhang Y, Chau R, Gerwick WH, Müller R & Neilan BA*. High titer heterologous production of lyngbyatoxin in E. coli, a protein kinase C activator from an uncultured marine cyanobacterium. ACS Chem Biol. 2013, 8(9):1888-1893 (SCI, 5-year IF: 5.6).

16. Bian X, Fu J, Plaza A, Herrmann J, Pistorius D, Lou H, Stewart F A, Zhang Y* & Müller, R*. In vivo evidence for a prodrug activation mechanism during colibactin maturation. ChemBioChem. 2013, 14(10):1194-1197(SCI, 5-year IF: 3.3).

17. Bian X, Plaza A, Zhang Y* & Muller R*. Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli. J Nat Prod. 2012, 75(9):1652-1655 (Selected as the Best Paper of 2012 in the Journal of Natural Products). (SCI, 5-year IF: 3.3, 2013 IF: 3.9)

18. Bian X, Huang F, Stewart F A, Xia L, Zhang Y* & Müller R*. Direct cloning, genetic engineering, and heterologous expression of the syringolin biosynthetic gene cluster in E. coli through Red/ET recombineering. ChemBioChem. 2012, 13 (13): 1946-1952 (SCI, 5-year IF: 3.3).

19. Fu J, Bian X, Hu S, Wang H, Huang F, Seibert P M, Plaza A, Xia L, Müller R, Stewart F A & Zhang Y*. Enhanced direct DNA cloning by full length RecE and its application to bioprospecting for secondary metabolites. Nat Biotechnol. 2012. 30(5):440-446 (SCI, 5-year IF: 35.6, 2013 IF 39.08).

20. Bird AW, Erler A, Fu J, Hériché JK, Maresca M, Zhang Y, Hyman AA* & Stewart AF*. High-efficiency counterselection recombineering for site-directed mutagenesis in bacterial artificial chromosomes. Nat Methods. 2011, 9(1):103-109 (SCI, 5-year IF: 27.2).

PATENTS

1. Bian X, Müller R, Fu J, Stewart F A, Zips D and Zhang Y, Heterologous expression of PKS/NRPS gene cluster and targeted anticancer drug delivery. (2010), International patent application No: PCT/IB2010/055923

2. Stewart AF, Fu J, and Zhang Y, Method of nucleic acid recombination. (2009), International patent application No: PCT/IB2009/000780

3. Zhang Y, Müller R, Stewart AF, Wenzel S, Gross F and Fu J. Methods for heterologous expression of secondary metabolites. (2005) International patent application No: PCT/IB2005/003650,.issued in UK on August, 2008

4. Stewart AF, Zhang Y and Buchholz F. Novel DNA cloning method. (1997) US patent No. 6,509,156, issued on January 21, 2003. European patent No. 1291420, issued on March 12, 2003.

5. Stewart AF, Zhang Y and Muyrers JPP. Methods and compositions for directed cloning and subcloning using homologous recombination. (1999) United States Patent No. 6,355,412 , issued on 12th of March, 2002

6. Zhang Y, Stewart AF and Muijrers JP.P.. Improved RecT or RecET cloning and subcloning method. (2001) European Patent Application No. 01 117 529.6

7. Stewart AF, Zhang Y and Muyrers JPP. Recombination method. (2001) European Patent Application No. 0103276.2

8. Stewart AF, Zhang Y and Hallet B. Use of a tyrosine recombinase for genetic engineering. (2000). International patent application number: PCT/EP02/07176. Issued in 2005.

9. Nawroth P, Nakagawa K and Zhang Y. Tissue factor for influencing blood vessel formation. (1997). U.S. Patent 6,930,094, Issued on 16th of August, 2005.


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