高通量筛选与编辑平台实验室(王猛组)依托于研究所大型自动化装备,通过对生物学研究操作过程的高通量化与自动化使得人力从繁琐的重复工作中解放出来,同时也通过完成人力不可能完成的大量实验实现从数量到质量的突变,能把生物学研究推向一个新的高峰。国际上高通量筛选从设备到技术远没有达到系统化与标准化,正处于高速发展百家争鸣的阶段。研究组现阶段在高通量筛选平台的工作主要集中于将生物学研究的核心实验操作实现高通量自动化。如实现微生物DNA转化的高通量自动化;质粒库、菌种突变库的高通量自动化构建;菌种的自动化改造,小分子化合物的高通量检测等。另一方面研究组主要运用合成生物学、分子生物学、生物化学及高通量生物技术等手段,开展围绕生物活性分子的发掘、生物合成机理、高效生产为核心问题的基础及应用技术研究。研究成果在Nat Commun, Trends Biotechnol, ACS Catal, Meta Eng等国际一流杂志上发表31篇文章。申请专利6项。
代表论著
1. Ran Tu, Yue Zhang, Erbing Hua, Likuan Bai, Huamei Huang, Kaiyue Yun, Meng Wang*,(2021) Droplet-based microfluidic platform for high-throughput screening of Streptomyces. Commun Biol, Accepted
2. 卢挥 张启 于思礼 王钰 康明 韩双艳 刘叶* 王猛,(2021)谷氨酸棒杆菌中基于CRISPR/Cas9的多位点碱基编辑系统的优化 .生物工程学报
3. Yue Zhang, Kaiyue Yun, Huamei Huang, Ran Tu, Erbing Hua*, Meng Wang*,(2021)Antisense RNA Interference-Enhanced CRISPR/Cas9 Base Editing Method for Improving Base Editing Efficiency in Streptomyces lividans 66. ACS Synth Biol. doi: 10.1021/acssynbio.0c00563
4. Yu Wang*, Haijiao Cheng, Yang Liu, Ye Liu, Xiao Wen, Kun Zhang, Xiaomeng Ni, Ning Gao, Liwen Fan, Zhihui Zhang, Jiao Liu, Jiuzhou Chen, Lixian Wang, Yanmei Guo, Ping Zheng*, Meng Wang*, Jibin Sun and Yanhe Ma,(2021) In-situ generation of large numbers of genetic combinations for metabolic reprogramming via CRISPR-guided base editing. Nat Commun, 12(1):678.
5. Yu Wang*, Ye Liu, Ping Zheng, Jibin Sun and Meng Wang*,(2020) Microbial Base Editing: A Powerful Emerging Technology for Microbial Genome Engineering. Trends Biotechnol, S0167-7799(20)30174-8
6. Sili Yu, Marcus A. Price Yu Wang, Yang Liu, Yanmei Guo, Xiaomeng N, Susan J. Rosser, Changhao Bi* and Meng Wang*, (2020) CRISPR-dCas9 mediated cytosine deaminase base editing in Bacillus subtilis. ACS Synth Biol. 9(7):1781-1789
7. 黄华媚 白立宽 刘叶 李俊维 王猛* 花尔并* ,(2019) BE3 型胞嘧啶碱基编辑器在谷氨酸棒杆菌中的开发及应用. 生物技术通报 36(3)
8. Xiaoting Lan, Wei Yuan, Meng Wang*, Han Xiao*. (2019). Efficient biosynthesis of antitumor ganoderic acid HLDOA using a dual tunable system for optimizing the expression of CYP5150L8 and a Ganoderma P450 reductase. Biotechnol Bioeng 116(12):3301-3311
9. 李俊维 刘叶 王钰 郁彭 郑平 王猛*, (2019) 谷氨酸棒杆菌碱基编辑的条件优化, 生物工程学报 DOI:10.13345/j.cjb.190192
10. Yu Wang, Ye Liu, Junwei Li,1, Yi Yang, Xiaomeng Ni, Haijiao Cheng, Teng Huang, Yanmei Guo, Hongwu Ma, Ping Zheng*, Meng Wang*, Jibin Sun, Yanhe Ma, (2019). Expanding targeting scope, editing window, and base transition capability of base editing in Corynebacterium glutamicum. Biotechnol Bioeng, 116(11):3016-3029
11. Han Xiao*, Yue Zhang#, Meng Wang*,(2018)Discovery and engineering of cytochrome P450s for terpenoid biosynthesis,Trends Biotechnol. pii: S0167-7799(18)30318-4
12. 崔金明 张炳照 马迎飞 傅雄飞 王 猛 刘陈立*,(2018)合成生物学研究的工程化平台,中国科学院院刊 11:1249-1257
13. Graham Heberlig, Jesse T. C. Brown, Ryan Simard, Monica Wirz, Wei Zhang, Meng Wang, Leah I Susser, Mark E Horsman, Christopher Noyce Boddy*, (2018) Chemoenzymatic Macrocycle Synthesis Using Resorcylic Acid Lactone Thioesterase Domains. Org. Biomol. Chem. DOI:10.1039/C8OB01512K
14. Yu W, Ye L, Jiao L, Yanmei G, Liwen F, Xiaomeng N, Xiaomei Z , Meng W*, Ping Z*, Jibin S*, Yanhe M,(2018)MACBETH: multiplex automated Corynebacterium glutamicum base editing method. Metabolic Engineering. May 47:200-210
15. Yang L, Ye L, Meng W* (2017). Design, optimization and application of small molecule biosensor in metabolic engineering. Frontiers in Microbiology. Oct 17;8:2012
16. Wang, M., Zhao, H. (2016). Combined and Iterative Use of Computational Design and Directed Evolution for Protein-Ligand Binding Design. Methods in Molecular Biology. 1414:139-53.
17. Wang, M., Yu, C., Zhao, H. (2016). Identification of an important motif that controls the activity and specificity of sugar transporters. Biotechnology and Bioengineering. 113(7):1460-7
18. Wang, M., Yu, C., Zhao, H. (2016). Directed evolution of xylose specific transporters to facilitate glucose-xylose co-utilization. Biotechnology and Bioengineering. 113(3):484-91
19. Li, S., Si, T., Wang, M., Zhao, H. (2015). Development of a Synthetic Malonyl-CoA Sensor in Saccharomyces cerevisiae for Intracellular Metabolite Monitoring and Genetic Screening. ACS synthetic biology. DOI:10.1021/acssynbio.5b00069
20. Wang, M., Li, S., Zhao, H. (2015). Design and engineering of intracellular-metabolite-sensing/regulation gene circuits in Saccharomyces cerevisiae. Biotechnology and Bioengineering. DOI: 10.1002/bit.25676
21. Wang, M., Zhao, H. (2014) Characterization and engineering of the adenylation domain of a NRPS-like protein: a potential biocatalyst for aldehyde generation. ACS catalysis, 4(4), 1219-1225.
22. Heberlig, G.W., Wirz, M., Wang, M., and Boddy, C. N. (2014). Resorcylic acid lactone biosynthesis relies on a stereo-tolerant macrocyclizing thioesterase. Organic Letters, 16(22), 5858-5861.
23. Wang, M., Beissner, M.; Zhao, H. (2013) Aryl-aldehyde formation in fungal polyketides: Discovery and characterization of a distinct biosynthetic mechanism. Chemistry & Biology. 21(2), 257-263.
24. Luo, Y., Huang, H., Liang, J., Wang, M., Lu, L., Shao, Z., Cobb, R.E., and Zhao, H. (2013) Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster. Nature Communications. 4, 2894.
25. Pinto, A., Wang, M., Horsman, M., Boddy, C. N. (2012) 6-Deoxyerythronolide B synthase thioesterase-catalyzed macrocyclization is highly stereoselective. Organic Letters, 14(9), 2278-2281.
26. Wang, M., Si, T. and Zhao, H. (2011) Biocatalyst development by directed evolution. Bioresource Technology, 115,117-125.
27. Wang, M. and Zhao, H. (2011) Microbial synthesis of drugs and fuels via synthetic biology. Chinese Bulletin of Life Sciences, 23, 875-881.
28. Wang, M., Zhou, H., Wirz, M., Tang Y. and Boddy, C.N. (2009) A thioesterase from an iterative fungal polyketide synthase shows macrocyclization and cross coupling activity and may play a role in controlling iterative cycling through product offloading. Biochemistry 48 (27), 5288–6290.
29. Wang, M., Opare, P. and Boddy, C. N. (2009) Polyketide synthase thioesterases catalyze rapid hydrolysis of peptidyl thioesters. Bioorganic and Medicinal Chemistry Letter 19 (5), 1413-1415.
30. Wang, M. and Boddy, C. N. (2008) Examining the role of hydrogen bonding interactions in the substrate specificity for the loading step of polyketide synthase thioesterase domains. Biochemistry 47 (45), 11793–11803.
31. Wu, Q., Wang, M., Chen, Z. C., Lu, D. S., Lin, X. F. (2006) Enzymatic synthesis of metronidazole esters and their monosaccharide ester derivatives. Enzyme Microbiology and Technology 39 (6), 1258-1263.