医药微生物技术

李盛英

教授
博士/硕士生导师
0532-58632466
个人简介 科研项目 学术论文 其他介绍

教育背景

博士:2004.09-2009.12,美国密西根大学药学院,药物化学系

硕士:2000.09-2003.07,厦门大学生命科学学院,微生物与生物技术系

学士:1996.09-2000.07,厦门大学生命科学学院,生物学基地班


工作经历?

起止时间 单位名称 专业技术职务

2018.11至今,微生物技术国家重点实验室,山东大学,教授

2012.06-2018.10,中国科学院青岛生物能源与过程研究所,研究员

2010.01-2012.05,美国密西根大学生命科学学院,博士后;参与创立生物技术公司Alluvium Biosciences Inc.,并担任生化部总监

2003.09-2004.08,厦门大学生命科学学院,研究助理


研究方向

1.微生物天然产物生物合成

2. P450酶学与酶工程

3.工业微生物菌株改良

科研项目

1. 2019.12-2024.11,合成塑料高效生物降解的关键技术—课题1—合成塑料降解菌/酶的筛选及鉴定,2019YFA0706901,课题负责人。

2. 2019.08-2024.07,碳-氢键选择性氧化P450酶的人工设计,山东省自然科学基金重大基础研究项目,ZR2019ZD20,主持。

3. 2019.01-2022.12,创建精准模拟人类肝脏CYPs生理行为的酵母人工肝,国家自然科学基金面上项目,NSFC 31872729,主持。

4. 2018.03-2020.02,耦合非天然辅酶的P450脂肪酸衍生细胞工厂,大连化物所—青岛能源所融合基金,DICP&QIBEBT UN201706,主持。

5. 2017.08-2019.07,基于P450催化元件的高值天然产物生物合成途径重构,山东省自然科学基金重大基础研究项目,ZR2017ZB0207,主持。

6. 2017.09-2019.09,Proof of Concept of Pathway Integration for α-Olefin Biosynthesis in Photosynthetic Microorganisms, TOTAL, Research Program Agreement between TOTAL Marketing Services and QIBEBT,国际合作项目,主持。

7. 2018.01-2018.12,一株热带海洋链霉菌活性天然产物资源的深度挖掘,国家自然科学基金应急管理项目,NSFC 81741155,主持。

8. 2016.01-2020.12,碳-氢键选择性氧化P450酶的人工设计研究,中科院前沿科学重点研究计划,QYZDB-SSW-SMC042,主持。

9. 2016.01-2020.12,碳-氢键选择性氧化P450酶的设计与应用,中国科学院青岛生物能源与过程研究所重点培育方向项目,主持。

10. 2015.10-2017.03,Improving C12 activity of new decarboxylase encoding sequences, TOTAL, Research Program Agreement between TOTAL Marketing Services and QIBEBT,国际合作项目,主持。

11. 2015.01-2017.12,微生物次级代谢产物生物合成,国家自然科学基金优秀青年基金项目,NSFC 31422002,主持。

12. 2015.01-2018.12,真菌生物碱Brevianamides的生物合成机制与合成生物学研究,国家自然科学基金面上项目,NSFC 21472204,主持。

13. 2015.01-2017.12,微生物生物合成,山东省杰出青年基金项目,JQ201407,主持。

14. 2013.10-2014.09,Production of α-alkenes with aviation fuel properties inEscherichia coli, BOEING, QIBEBT Collaboration Agreement for a Joint Research Laboratory for Sustainable Aviation Biofuels,国际合作项目,主持。

15. 2013.01-2016.12,一种P450脂肪酸脱羧酶的酶学、酶工程及组合生物合成研究,国家自然科学基金面上项目,NSFC 31270855,主持。

代表性论文

1. Ye, Y. #, Du, L. #, Zhang, X.,Newmister, S. A.,McCauley, M.,Alegre-Requena, J. V., Zhang, W., Mu, S.,Minami, A.,Fraley, A. E.,Adrover-Castellano, M. L.,Carney, N. A., Shende, V. V., Qi, F.,Oikawa, H., Kato, H.,Tsukamoto, S., Paton, R. S.,Williams, R. M.*, Sherman, D. H.*, andLi, S.* Fungal-derived Brevianamide assembly by a stereoselective semi-pinacolase.Nat. Catal.(Accepted)

2. Li, S.*, Du, L., and Bernhardt, R.* Redox partners: Function modulators of bacterial P450 enzymes.Trends Microbiol. 2020, doi.org/10.1016/j.tim.2020.02.012.

3. Jiang, Y., Li, Z., Zheng, S., Xu, H., Zhou, Y. J., Gao, Z., Meng, C. *, andLi, S.* Establishing an enzyme cascade for one-pot production of α-olefns from low-cost triglycerides and oils without exogenous H2O2 addition.Biotechnol. Biofuels 2020, 13, 52.

4. Xu, H., Liang, W., Ning, L., Jiang, Y., Yang, W., Wang, C., Qi, F., Ma, L., Du, L., Fourage, L., Zhou, Y. J. andLi, S.* Directed Evolution of P450 Fatty Acid Decarboxylases via High-Throughput Screening towards Improved Catalytic Activity.ChemCatChem 2019, 11, 1-6..

5. Liu, K., andLi, S.* Biosynthesis of fatty acid derived hydrocarbons: perspectives on enzymology and enzyme engineering,Curr. Opin. Biotech.2019, 62, 7-14.

6. Zhang, W., Du, L., Qu, Z., Zhang, X., Li, F., Li, Z., Qi, F., Wang, X., Jiang, Y., Men, P., Sun, J., Cao, S., Geng, C., Qi, F., Wan, X., Liu, C., andLi, S.* Compartmentalized Biosynthesis of Mycophenolic Acid.Proc. Natl. Acad. Sci. U.S.A. 2019, 116(27), 13305-13310.

7. Jiang, Y., Li, Z., Wang, C., Zhou, Y. J., Xu, H.*, andLi, S.*Biochemical characterization of three newα-olefn-producing P450 fatty acid decarboxylases with a halophilic property.Biotechnol. Biofuels 2019, 12, 79.

8. Zhang, W. #, Du, L. #, Li, F., Zhang, X., Qu, Z., Han, L., Li, Z., Sun, J., Qi, F., Yao, Q., Sun, Y., Geng, C.,Li, S.* Mechanistic insights into interactions between bacterial class I P450 enzymes and redox partners.ACS Catal. 2018, 8, 9992-10003.

9. Jiang, Y.,Li, S.* The catalytic function and application of cytochrome P450 enzymes in biosynthesis and organic synthesis.Chin. J. Org. Chem. 2018,38(9), 2307-2323.

10. Qi, F. #, Lei, C. #, Li, F., Zhang, X., Wang, J., Zhang, W., Fan, Z., Li, W., Tang, G., Xiao, Y.*, Zhao, G.,Li, S. * Deciphering the late steps of rifamycin biosynthesis.Nat. Commun.2018, 9,2342.

11. Chen, H., Meng, X., Xu, X., Liu, W.,Li, S. *The molecular basis for lipase stereoselectivity.Appl. Microbiol. Biotechnol. 2018,102(8),3487-3495.

12. Xu, H., Ning, L., Yang, W., Fang, B., Wang, C., Wang, Y., Xu, J., Colin, S., Laeuffer, F., Fourage, L., andLi, S. * In vitrooxidative decarboxylation of free fatty acids to terminal alkenes by two new P450 peroxygenases.Biotechnol. Biofuels2017, 10,208.

13. Zhang, X., andLi, S.* Expansion of chemical space for natural products by uncommon P450 reactions.Nat. Prod. Rep. 2017, 34(9), 1061-1089.

14. Du, L. #, Dong, S. #, Zhang, X., Jiang, C., Chen, J., Yao, L., Wang, X., Wan, X., Liu, X., Wang, X., Huang, S., Cui, Q., Feng, Y. *, Liu, S.*, andLi, S.*Selective oxidation of aliphatic C–H bonds in alkylphenols by a chemomimetic biocatalytic system.Proc. Natl. Acad. Sci. U.S.A. 2017,114(26), E5129-E5137.

15. Li, Z., Du, L., Zhang, W., Zhang, X., Jiang, Y., Liu, K., Men, P., Xu, H., Fortman, J. L., Sherman, D. H., Yu, B., Gao, S.,Li, S.* Complete elucidation of the late steps of bafilomycin bios ynthesis inStreptomyces lohii.J. Biol. Chem. 2017,292(17), 7095-7104.

16. Fang, B. #, Xu, H. #, Liu, Y., Qi, F., Zhang, W., Chen, H., Wang, C., Wang, Y., Yang, W., andLi, S.* Mutagenesis and redox partners analysis of the P450 fatty acid decarboxylase OleTJE.Sci. Rep.2017, 7, 44258.

17. 孙月, 马莉, 陈辉, 徐卉芳, 郑贤良, 齐凤霞, 李盛英*. 脂肪酶—P450脂肪酸脱羧酶融合蛋白催化的α烯烃合成[J].科学通报, 2017, 62(31), 3576-3582.

18. Sun, Y. #, Ma, L. #, Han, D. #, Du, L., Qi, F., Zhang, W., Sun, J., Huang, S., Kim, E.-S.,* andLi, S.* In vitro reconstitution of the cyclosporine specific P450 hydroxylases using heterologous redox partner proteins. J. Ind. Microbiol. Biotechnol.2016, 44(2),161-166.

19. Zhang, X., Li, Z., Du, L., Chlipala, G. E., Lopez, P. C., Zhang, W., Sherman, D. H.*, andLi, S.* Identification of an unexpected shunt pathway product provides new insights into tirandamycin biosynthesis.Tetrahedron Lett. 2016, 57(52), 5919-5923.

20. Zheng, X., Fang, B., Han, D., Yang, W., Qi,F., Chen, H., andLi, S.* Improving the Secretory Expression of an α-Galactosidase fromAspergillus niger in Pichia pastoris.PLoS ONE 2016,11(8), e0161529.

21. Du, L., Ma, L., Qi, F., Zheng, X., Jiang, C., Li, A., Wan, X., Liu, S.-J.*, andLi, S.* Characterization of a unique pathway for 4-cresol catabolism initiated by phosphorylation inCorynebacterium glutamicum. J. Biol. Chem. 2016, 291(12), 6583-6594.

22. 李众, 张伟, 李盛英*. 细胞色素P450酶与微生物药物创制[J].微生物学报, 2016, 56(3), 496-515.

23. Ma, L., Du, L., Chen, H., Sun, Y., Huang, S., Zheng, X., Kim, E.-S.*, andLi, S.*Reconstitution of the in vitro activity of the cyclosporine-specific P450 hydroxylase fromSebekia benihana and development of a heterologous whole cell biotransformation system. Appl. Environ. Microbiol. 2015, 81(18), 6268-6275.

24. Yan, J.*, Liu, Y., Wang, C., Han, B., andLi, S.*Assembly of lipase and P450 fatty acid decarboxylase to constitute a novel biosynthetic pathway for production of 1-alkenes from renewable triacylglycerols and oils.Biotechnol. Biofuels 2015, 8, 34.

25. Zhang, W., Cao, S., Qiu, L., Qi, F., Li, Z., Yang, Y., Huang, S., Bai, F., Liu, C., Wan, X.,* andLi, S.* Functional Characterization of MpaG’, theO-Methyltransferase Involved in the Biosynthesis of Mycophenolic Acid.Chembiochem 2015, 16(4), 565-569.

26. Yan, J.*, Zheng, X., Du, L., andLi, S.* Integrated lipase production and in situ biodiesel synthesis in a recombinant Pichia pastoris yeast: an efficient dual biocatalytic system composed of cell free enzymes and whole cell catalysts.Biotechnol. Biofuels 2014, 7, 55.

27. Zhang, W., Liu, Y., Yan, J., Cao, S., Bai, F., Yang, Y., Huang, S., Yao, L., Anzai, Y., Kato, F., Podust, L. M., Sherman, D. H.*, andLi, S.* New reactions and products resulting from alternative interactions between the P450 enzyme and redox partners.J. Am. Chem. Soc.?2014, 136(9), 3640-3646. (Faculty of 1000 Prime: http://f1000.com/prime/718276150)

28. Liu, Y., Wang, C., Yan, J., Zhang, W., Guan, W., Lu, X., andLi, S.* Hydrogen peroxide-independent production ofα-alkenes by OleTJE P450 fatty acid decarboxylase.Biotechnol. Biofuels 2014, 7, 28.

29. Yan, J.*, Zheng, X., andLi, S.* A novel and robust recombinantPichia pastoris yeast whole cell biocatalyst with intracellular overexpression of aThermomyces lanuginosus lipase: preparation, characterization and application in biodiesel production.Bioresour. Technol. 2014, 151, 43-48.

30. Zhang W., Fortman, J. L., Carlson, J. C., Yan, J., Liu, Y., Bai, F., Guan, W., Jia, J., Matainaho, T., Sherman, D. H.*, andLi, S.* Characterization of the bafilomycin biosynthetic gene cluster fromStreptomyces lohii.Chembiochem, 2013, 14(3), 301-306.

31. Li, S., Tietz, D. R., Rutaganira, F. U., Kells, P. M., Anzai, Y., Kato, F., Pochapsky, T. C., Sherman, D. H., and Podust, L. M.*Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin hydroxylation and epoxidation reactions.J. Biol. Chem. 2012, 287(45), 37880-37890.

32. Li, S., Anand, K., Tran, H., Yu, F., Finefield, J. M., Sunderhaus, J. D., McAfoos, T. J., Tsukamoto, S., Williams, R. M.*, and Sherman, D. H.*Comparative analysis of the biosynthetic systems for fungal bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide, paraherquamide and malbrancheamide pathways.MedChemComm 2012, 3(8), 987-996.

33. Li, S., Finefield, J. M., Sunderhaus, J. D., McAfoos, T. J., Williams, R. M.*, and Sherman, D. H.*Biochemicalcharacterization of NotB as an FAD-dependentoxidase in thebiosynthesis ofnotoamideindolealkaloids.J. Am. Chem. Soc.2012, 134(2), 788-791.

34. Carlson, J. C.#,Li, S. #, Gunatilleke, S. S., Anzai, Y., Burr, D. A., Podust, L. M., and Sherman, D. H.* Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes.Nat. Chem.2011, 3(8), 628-633.

35. Carlson, J. C. #,Li, S.#, Douglas, A. B., and Sherman, D. H.*Isolation and characterization of tirandamycins from a marine-derivedStreptomyces sp.J. Nat. Prod. 2009, 72(11), 2076-2079.

36. Li, S., Chaulagain, M. R., Knauff, A. R., Podust, L. M., Montgomery, J.*, and Sherman, D. H.* Selective oxidation of carbolide C-H bonds by an engineered macrolide P450 monooxygenase.Proc. Natl. Acad. Sci. U.S.A. 2009, 106(44), 18463-18468.

37. Li, S.,Anzai, Y., Kinoshita, K., Kato, F., Sherman, D. H.* Functional analysis of MycE and MycF, twoO-methyltransferases involved in the biosynthesis of mycinamicin macrolide antibiotics.Chembiochem 2009, 10(8), 1297-1301.

38. Li, S., Ouellet, H.,Sherman, D. H., Podust, L. M.* Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC fromStreptomyces venezuelae.J. Biol. Chem. 2009, 284(9), 5723-5730.

39. Anzai, Y. #,Li, S. #, Chaulagain, M. R., Kinoshita, K., Kato, F., Montgomery, J., Sherman, D. H.*Functional analysis of MycCI and MycG, cytochrome P450 enzymes involved in biosynthesis of mycinamicin macrolide antibiotics.Chem. Biol. 2008, 15(9), 950-959.

40. Li, S., Podust, L. M., Sherman, D. H.*Engineering and analysis of a self-sufficient biosynthetic cytochrome P450 PikC fused to the RhFRED reductase domain.J. Am. Chem. Soc. 2007, 129(43), 12940-12941.

41. Li, S., Grüschow, S., Dordick, J. S., Sherman, D. H.*Molecular analysis of the role of tyrosine 224 in the active site ofStreptomyces coelicolor RppA, a bacterial type III polyketide synthase.J. Biol. Chem. 2007, 282(17), 12765-12772.

42. Li, S., Wang, J., Zheng, Z., Xu, Q., Huang, Y., Zhao, Y., Su, W.*1-(2,4-Dihydroxy-3,5-Dimethylphenyl)-ethanone (Clavatol).Acta. Cryst. 2003, E59, o1649-o1650.

43. 李盛英, 郑忠辉*. 国外海洋抗肿瘤活性物质的研究与开发[J].海洋通报,2003, 22(2), 76-82.

获奖情况

1. 2019.11, ICBS-2019 Young Chemical Biologist Award

2. 2014.08, The National Science Fund for Excellent Young Scholars (优青)

3. 2011.09, Michigan Memorial Phoenix Energy Institute (MMPEI) Postdoctoral Fellowship

4. 2010.04, National Award for Outstanding Chinese PhD Student Abroad 2009

5. 2005.12, NR-BLAKE, MR. AND MRS. EDWARD Fellowship, College of Pharmacy, The University of Michigan


所获专利

1. Chimeric Cytochrome P450 Proteins and Methods of Use.LI, Shengying, and SHERMAN, David H. (US 20090081758A1)

2. A Method for Selective Oxidation of C-H Bonds by an Engineered P450 Enzyme.LI, Shengying, SHERMAN, David H., CHAULAGAIN, Mani Raj, MONTGOMERY, John, and KNAUFF, Allison R. (WO 2011038313A2)

3. Biosynthetic Systems Producing Fungal Indole Alkaloids LI, Shengying, David H. Sherman, Krithika Anand, andRobert M. Williams (AuthorizationNo.: US 9650656 B2)

4. 阎金勇,李盛英。一种利用偶联生产脂肪酶的方式催化生产生物柴油的方法(申请号:201410138507.3,申请公布号:CN103923954A)

5. 李盛英,刘奕,吕雪峰,刘旭峰。一种生产脂肪端烯的方法及其应用(申请号:201410660346.4)

6. 阎金勇,李盛英。一种基于脂肪酶与P450脂肪酸脱羧酶偶联催化的脂肪烯烃催化合成方法(申请号:201510003451.5,申请公布号:CN104561152A,授权号:ZL201510003451.5)

7. 李盛英,马莉,Eung-Soo Kim。一种制备毛发生长促进剂的生物转化方法(申请号:201510346350.8,申请公布号:CN106319007A,授权号:ZL201510346350.8)

8. 李盛英,杜磊,刘双江。一种酚类化合物催化氧化系统及其应用(申请号:201610015698.3)

9. 李盛英,郑贤良。高效分泌表达黑曲霉α-半乳糖苷酶AGA的工程菌及其构建和应用(申请号:2015107066150,申请公布号:CN105219791A)

10. 李盛英,房博,齐凤霞,张伟,杜磊。支撑P450脂肪酸脱羧酶活性的还原伴侣蛋白组合及其应用(申请号:201610151612.X,申请公布号:CN107201356A)

11. Production of Alpha-Olefins. Fourage Laurent, Laeuffer Frederie, Strub Henri, Wang Yun, Xu Jian, Xu Huifang, Li Shengying.( AuthorizationNo.: US 10407638B2)

12. Method for detecting hydrogen peroxide conversion activity of an enzyme. Li Shengying, Xu Huifang, Ning Linlin.(?EP17290115.9)

13. Improved cytochrome P450 fatty acid decarboxylases. Li Shengying, Xu Huifang, Ning Linlin.( EP18290089.4)

14. 李盛英,李众,杜磊,张兴旺,张伟。一种巴弗洛霉素高产工程菌及其构建和应用(申请号:201811634377.7)

15. 李盛英,李众。一类四环二萜类化合物及其制备方法与应用(申请号:201911072144.7)