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  研究员
 
姓名  
孙周通
性别  
专家类别  
N/A
职称  
研究员
学历  
博士研究生
电话  
022-84861981
传真  
N/A
电子邮件  
sunzht@tib.cas.cn
地址  
天津空港经济区西七道32号
邮编  
300308

简历

1. 教育经历

  2005.9-2011.12, 中国科学院上海生命科学研究院,微生物学,博士

  2003.9-2005.6, 河南大学, 生物工程, 工学学士

  2000.9-2003.6, 河南牧业经济学院, 生物技术  

2. 工作经历

  2016.9-至今, 中国科学院天津工业生物技术研究所,研究员

  2013.10-2016.9, 德国马普煤炭研究所/菲利普马尔堡大学,博士后

  2012.10-2013.9, 新加坡南洋理工大学,博士后研究员

  2012.1-2012.9, 中国科学院上海生命科学研究院/上海工业生物技术研发中心,助理研究员/项目主管

  2008.7-2011.12, 上海工业生物技术研发中心,项目负责人(兼)

   2007.4-2008.6, 中国科学院上海生命科学研究院湖州工业生物技术中心,项目负责人(兼)


研究方向:
  

工业生物技术是人类应对环境问题、能源问题和资源问题的重要解决方案,酶是核心发动机,广泛应用于食品,医药,农产品加工等行业,是实现生物催化合成的基本功能单元。团队围绕工业酶设计与绿色生物催化,重点开展酶分子工程、化酶催化工程、生物合成工程等方向的基础与应用研究。

    

 

主要研究进展和学术贡献:

1)针对人工酶设计筛选瓶颈,聚焦氨基酸残基精准定位和密码子设计,建立了精简密码子设计体系模型,突破了筛选瓶颈,揭示了密码子设计原理。

2)针对酶催化机制,基于晶体结构解析与多尺度计算模拟,解析了底物特异识别与手性控制机制,为酶的理性设计奠定了基础。

3)针对工业酶精准设计应用,将分子构象动力学、脯氨酸诱导设计等策略用于酶的理性设计,实现了工业酶的精准设计与人工途径创建,构建了系列高效生物催化剂。

代表论著: 

论文    

2022

58. Ming H, Yuan B, Qu G*, Sun Z*. Engineering the activity of Amine Dehydrogenase in the Asymmetric Reductive Amination of Hydroxyl Ketones. Catal. Sci. Technol., 2022, DOI: 10.1039/D2CY00391K.

57. Jiang Y#, Li X#, Liu B, Tong F, Qu G*, Sun Z*. Engineering the hydrogen transfer pathway of an alcohol dehydrogenase to increase activity by rational enzyme design. Mol. Catal., 2022, 530, 112603.

56. Wang P, Han X, Liu X*, Lin R, Chen Y, Sun Z*, Zhang W*. Synthesis of Enantioenriched Sulfoxides by an Oxidation-Reduction Enzymatic Cascade. Chem. Eur. J.. 2022, e202201997.

55. Lu J, Wang Z, Jiang Y, Sun Z*, Luo W*. Modification of the substrate specificity of leucine dehydrogenase by site-directed mutagenesis based on biocomputing strategies. Syst. Microbiol. and Biomanuf., 2022. https://doi.org/10.1007/s43393-022-00116-5.

54. Sang X, Tong F, Zeng Z*, Wu M, Yuan B, Sun Z, Sheng X, Qu G, Alcalde M, Hollmann F, Zhang W*. A Biocatalytic Platform for the Synthesis of Enantiopure Propargylic Alcohols and Amines. Org. Lett., 2022, 24(23), 4252-4257.

53. Qin Z, Zhang X, Sang X, Zhang W, Qu G*, Sun Z*. Carboxylic acid reductases enable intramolecular lactamization reactions. Green Synth. Catal., 2022. https://doi.org/10.1016/j.gresc.2022.05.009.

52. Wang J#, Qu G#, Xie L, Gao C, Jiang Y, Zhang YPJ, Sun Z*, You C*. Engineering of a thermophilic dihydroxy-acid dehydratase toward glycerate dehydration for in vitro biosystems. Appl. Microbiol. Biotechnol., 2022, 106, 3625-3637.

51. Li Y, Zhang P, Sun Z, Li H, Ge R, Sheng X, Zhang W*. Peroxygenase-Catalyzed Selective Synthesis of Calcitriol Starting from Alfacalcidol. Antioxidants, 2022, 11, 1044.

50. Zhang J#, Liao D#, Chen R#, Zhu F, Ma Y, Gao L, Qu G, Cui C,  Sun Z*, Lei X*, Gao S*. Tuning an Imine Reductase for the Asymmetric Synthesis of Azacycloalkylamines by Concise Structure-Guided Engineering. Angew. Chem. Int. Ed., 2022. e202201908.

49. Song S#, Jiang Y#, Chen R, Su W, Liang W, Yang D, Li J, Zhang W, Gao S, Yuan B*, Qu G*, Sun Z*. Whole-cell Biotransformation of Penicillin G by a Three-enzyme Co-expression System with Engineered Deacetoxycephalosporin C Synthase. ChemBioChem, 2022, e202200179.

48. Yang D, Su W, Jiang Y, Gao S, Li X, Qu G*, Sun Z*. Biosynthesis of β-lactam nuclei in yeast. Metab. Eng., 2022, 72, 56-65.

47. 毕悦欣,蒋迎迎,覃宗敏,曲戈*孙周通*.醇脱氢酶金属离子绑定位点的可替换性. 生物工程学报, 2022. https://doi.org/10.13345/j.cjb.210601

46. Jiang Y#, Qu G#, Sheng X, Tong F, Sun Z*. Unraveling the mechanism of enantio-controlling switches of an alcohol dehydrogenase toward sterically small ketone. Catal. Sci. Technol., 2022, 12, 1777-1787.

45. Qu G,  Bi Y, Liu B, Li JK, Han X, Liu W, Jiang Y, Qin Z, Sun Z*. Unlocking the Stereoselectivity and Substrate Acceptance of Enzymes: Proline Induced Loop Engineering Test. Angew. Chem. Int. Ed., 2022, 61 (1), e202110793.

44. Bi H#, Qu G#, Wang S, Zhuang Y, Sun Z*, Liu T*, Ma Y. Biosynthesis of a Rosavin Natural Product in Escherichia coli  by Glycosyltransferase Rational Design and Artificial Pathway Construction. Metab. Eng., 2022, 69, 15-25.

43. Dong C#, Qu G#,  Guo J#, Wei F, Gao S, Sun Z, Jin L, Sun X, Rochaix JD, Miao Y*, Wang R*. Rational design of geranylgeranyl diphosphate synthase enhances carotenoid production and improves photosynthetic efficiency in Nicotiana tabacum. Science Bulletin, 2022, 67(3), 315-327.

2021

42. Tong F#, Qin Z#, Wang H#, Jiang Y, Li J, Ming H, Qu G, Xiao Y*, Sun Z*. Biosynthesis of Chiral Amino Alcohols via an Engineered Amine Dehydrogenase in E. coli. Front. Bioeng. Biotechnol., 2021; 9: 778584.

41. Wu R, Yu Y,  Wang Y, Wang YZ, Song H, Ma C, Qu G, You C, Sun Z, Zhang W, Li A, Li CM*, Yong YC*, Zhu Z*. Wastewater-powered high-value chemical synthesis in a hybrid bioelectrochemical system. iScience, 2021, 103401.

40. 张发光, 曲戈, 孙周通*, 马军安*. 从化学合成到生物合成天然产物全合成新趋势. 合成生物学, 2021, 2(5), 674-696.

39. 张武元*, 袁波, 曲戈, 孙周通. 光促酶催化反应设计及生物合成应用. 生物学杂志 (J. Biol.), 2021, 38(5), 1-11. 特约综述

38. Li Y, Yuan B, Sun Z, Zhang W*. C–H bond functionalization reactions enabled by photobiocatalytic cascades. Green Synth. Catal., 2021, 2 (3), 267-274.

37. Chen Q, Guo M, Bi Y, Qu G, Sun Z, Wang Y*, Luo G. Whole-cell biocatalytic synthesis of S-(4-chlorophenyl)-(pyridin-2-yl) methanol in a liquid–liquid biphasic microreaction system. Bioresource Technol., 2021, 330: 125022.

36. Li J#, Qu G#, Shang N, Chen P, Men Y, Liu W, Mei Z, Sun Y*, Sun Z*. Near-perfect control of the regioselective glucosylation enabled by rational design of glycosyltransferases. Green Synth. Catal., 2021, 2, 45-53.

2020

35. Acevedo-Rocha, CG*, Hollmann F*, Sanchis J*, Sun Z*. A Pioneering Career in Catalysis: Manfred T. Reetz. ACS Catal., 2020, 10, 15123-15139. (invited)

34. Wang H#, Qu G#, Li JK#, Ma JA, Guo J, Miao Y, Sun Z*. Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols. Catal. Sci. Technol., 2020. 10, 5945-5952.

33. 蒋迎迎,曲戈,孙周通*. 机器学习助力酶定向进化. 生物学杂志 (J. Biol.), 2020, 37(4), 1-11. 特约综述

32. Mei Z#, Zhang K#, Qu G, Li JK, Liu B, Ma JA, Tu R*, Sun Z*. A High-Throughput Fluorescence Assay for Ketone Detection and its Applications in Enzyme Mining and Protein Engineering. ACS Omega, 2020, 5, 13588-13594.

31. Qu G#, Li A#, Acevedo-Rocha CG#, Sun Z*, Reetz MT*. The Crucial Role of Methodology Development in Directed Evolution of Selective Enzymes. Angew. Chem. Int. Ed., 2020, 59, 13204-13231. (invited)

30. Chen J#, Fan F#, Qu G#, Tang J, Xi Y, Bi C, Sun Z*, Zhang X*. Identification of Absidia orchidis steroid 11β-hydroxylation system and its application in engineering Saccharomyces cerevisiae for one-step biotransformation to produce hydrocortisone. Metab. Eng., 2020, 57, 31-42.

2019

29. 张锟#,曲戈#,刘卫东,孙周通. 工业酶结构与功能的构效关系. 生物工程学报 (Chin. J. Biotech.), 2019, 35(10): 1806-1818. (邀请综述)

28. Qu G#, Liu B#, Zhang K, Jiang Y, Zhai C, Guo J, Wang R, Miao Y, Sun Z*. Computer-assisted engineering of the catalytic activity of a carboxylic acid reductase. J. Biotechnol., 2019, 306, 97-104. (invited)

27.  曲戈#,朱彤#,蒋迎迎,吴边,孙周通*. 蛋白质工程:从定向进化到计算设计. 生物工程学报 (Chin. J. Biotech.), 2019, 35(10), 1843-1856. (邀请综述)

26. Li A#, Qu G#, Sun Z*, Reetz MT*. Statistical Analysis of the Benefits of Focused Saturation Mutagenesis in Directed Evolution Based on Reduced Amino Acid Alphabets. ACS Catal., 2019, 9, 7769-7778.

25.  Liu B#, Qu G#, Li J, Fan W, Ma JA, Xu Y, Nie Y*, Sun Z*. Conformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones. Adv. Synth. Catal., 2019, 361, 3182-3190.

24. Qu G#, Liu B#, Jiang Y, Nie Y, Yu H, Sun Z*. Laboratory evolution of an alcohol dehydrogenase towards enantioselective reduction of difficult-to-reduce ketones. Bioresour. Bioprocess. 2019, 6(1):18.

23. Sun Z*, Liu Q, Qu G, Feng Y*, Reetz MT*. The Utility of B-Factors in Protein Science: Interpreting Rigidity, Flexibility and Internal Motion and Engineering Thermostability. Chem. Rev., 2019, 119, 1626-1665.

22. Qu G#, Fu M#, Zhao L, Liu B, Liu P, Fan W, Ma J, Sun Z*. Computational Insights into the Catalytic Mechanism of Bacterial Carboxylic Acid Reductase. J. Chem. Inf. Model., 2019, 59, 832-841.

21. Dai Z#, Liu Y#, Sun Z#, Wang D, Qu G, Ma X, Fan F, Zhang L, Li S, Zhang X*. Identification of a novel cytochrome P450 enzyme that catalyzes the C-2α hydroxylation of pentacyclic triterpenoids and its application in yeast cell factories. Metab. Eng., 2019, 51, 70-78.

20. 曲戈,张锟,蒋迎迎,孙周通*. 2018诺贝尔化学奖:酶定向进化与噬菌体展示技术. 生物学杂志 (J. Biol.), 2019, 36(1): 1-6. 特约综述.

2018

19. Li A, Sun Z, Reetz MT*. Solid-Phase Gene Synthesis for Mutant Library Construction: The Future of Directed Evolution? ChemBioChem, 2018, 19 (19), 2023-2032. 

18. Qu G, Guo J, Yang D, Sun Z*. Biocatalysis of carboxylic acid reductases: Phylogenesis, Catalytic Mechanism and Potential Applications. Green Chem., 2018, 20(4), 777-792.

17. Qu G, Lonsdale R, Yao P, Li G, Liu B, Reetz MT*, Sun Z*. Methodology Development in Directed Evolution: Exploring Options When Applying Triple Code Saturation Mutagenesis. ChemBioChem, 2018, 19, 239-246.

16. Sun Z#, Wu L#, Bocola M, Chan H.C. S, Lonsdale R, Kong X.-D, Yuan S*, Zhou J*, Reetz MT*. Structural and Computational Insight into the Catalytic Mechanism of Limonene Epoxide Hydrolase Mutants in Stereoselective Transformations. J. Am. Chem. Soc., 2018, 140 (1), 310-318.

15. Qu G, Zhao J, Zheng P, Sun J, Sun Z*. Recent advances in directed evolution. Chin. J. Biotech., 2018, 34(1): 1-11.

曲戈,赵晶,郑平,孙际宾,孙周通*。定向进化技术的最新进展。生物工程学报, 2018, 34(1): 1-11. 特邀综述(双语)

14. Li A, Acevedo-Rocha CG, Sun Z, Cox T, Xu J, Reetz MT*. Beating Bias in Directed Evolution of Proteins: Combining High-Fidelity On-Chip Solid-Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial Library Construction. ChemBioChem, 2018, 19(3), 221-228.

13. Acevedo-Rocha CG*, Sun Z*, Reetz MT*. Clarifying the Difference between Iterative Saturation Mutagenesis as a Rational Guide in Directed Evolution and OmniChange as a Gene Mutagenesis Technique. ChemBioChem, 2018, 19 (24), 2542-2544.

12. Yang J#, Zhu Y#, Qu G, Zeng Y, Tian C, Dong C, Men Y, Dai L, Sun Z*, Sun Y*, Ma Y. Biosynthesis of dendroketose from different carbon sources using in vitro and in vivo metabolic engineering strategies. Biotechnol. Biofuels, 2018, 11, 290.

Before 2016

11. Sun Z#, Salas PT#, Siirola E#, Lonsdale R#, Reetz MT*. Exploring productive sequence space in directed evolution using binary patterning versus conventional mutagenesis strategies. Bioresour. Bioprocess, 2016, 3:44, 1-8.

10Li A, Ilie A, Sun Z, Lonsdale R, Xu JHReetz MT*. Whole-Cell-Catalyzed Multiple Regio- and Stereoselective Functionalizations in Cascade Reactions Enabled by Directed Evolution. Angew. Chem. Int. Ed., 2016, 55, 12026 -12029.

9. Sun Z#, Li G#, Ilie A#, Reetz MT*. Exploring the substrate scope of mutants derived from the robust alcohol dehydrogenase TbSADH. Tetrahedron Letters, 2016, 57, 3648-3651. (cover story)

8. Sun Z, Lonsdale R, Li G, Reetz MT*. Comparing Different Strategies in Directed Evolution of Enzyme Stereoselectivity: Single- versus Double-Code Saturation Mutagenesis. ChemBioChem, 2016, 17, 1865-1872.

7. Li G#, Zhang H#, Sun Z, Liu X*, Reetz MT*. Multiparameter Optimization in Directed Evolution: Engineering Thermostability, Enantioselectivity and Activity of an Epoxide Hydrolase. ACS. Catal., 2016, 6, 3679–3687.

6. Sun Z, Wikmark Y, B?ckvall J-E*, Reetz MT*. New Concepts for Increasing the Efficiency in Directed Evolution of Stereoselective Enzymes. Chem. Eur. J., 2016, 22, 5046-5054.

5. Sun Z, Lonsdale R, Ilie A, Li G, Zhou J, Reetz MT*. Catalytic Asymmetric Reduction of Difficult-to-Reduce Ketones: Triple Code Saturation Mutagenesis of an Alcohol Dehydrogenase. ACS. Catal., 2016, 6, 1598-1605.

4. Sun Z, Lonsdale R, Wu L, Li G, Li A, Wang J, Zhou J*, Reetz MT*. Structure-Guided Triple-Code Saturation Mutagenesis: Efficient Tuning of the Stereoselectivity of an Epoxide Hydrolase. ACS. Catal., 2016, 6, 1590-1597.

3. Sun Z, Ilie A, Reetz MT*. Towards the Production of Universal Blood by Structure-guided Directed Evolution of Glycoside Hydrolases. Angew. Chem. Int. Ed., 2015, 54, 9158-9160.

2. Sun Z, Lonsdale R, Kong XD, Xu JH, Zhou J*, Reetz MT*. Reshaping an Enzyme Binding Pocket for Enhanced and Inverted Stereoselectivity: Use of Smallest Amino Acid Alphabets in Directed Evolution. Angew. Chem. Int. Ed., 2015, 54, 12410-12415.

1. Sun Z, Ning Y, Liu L, Liu Y, Sun B, Jiang W, Yang C, Yang S*. Metabolic engineering of the L-phenylalanine pathway in Escherichia coli for the production of S- or R-mandelic acid. Microb. Cell Fact., 2011, 10:71. “highly accessed”

Invited Book chapters:

3. Qu G, Sun Z*. In silico prediction methods for site-saturation mutagenesis In “Enzyme Engineering: Methods and Protocols of Methods in Molecular Biology, Humana Press 2022, 2397, pp49-69.

Qu G., Sun Z. (2022) In Silico Prediction Methods for Site-Saturation Mutagenesis. In: Magnani F., Marabelli C., Paradisi F. (eds) Enzyme Engineering. Methods in Molecular Biology, vol 2397. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1826-4_4

2. Qu G, Sun Z*, Reetz MT*. Iterative Saturation Mutagenesis for Semi-rational Enzyme Design, Protein Engineering: Tools and Applications, Wiley 2021, pp105-132.

1. Sun Z, Reetz MT*. CHAPTER 12 Controlling the Regio- and Stereoselectivity of Cytochrome P450 Monooxygenases by Protein Engineering. In Dioxygen-dependent Heme Enzymes, The Royal Society of Chemistry: 2019; pp 274-291.

 

申请及授权发明专利

13. 孙周通、王红月、曲戈:一种双酶级联催化合成(R-3-氨基-1-丁醇的方法。ZL202011385203.9

12. 孙周通、曲戈、刘贝贝毕悦欣: 醇脱氢酶突变体及其在高效不对称还原制备手性双芳基醇化合物中的应用。ZL202011216302.4

11. 孙周通、王红月、曲戈、蒋迎迎:胺脱氢酶突变体及其在手性胺醇化合物合成中的应用。CN202010499781.9

10. 孙周通、杨大猛、曲戈、蒋迎迎、李超、刘保艳:脱乙酰氧头孢菌素C合成酶突变体及其在β-内酰胺抗生素母核合成中的应用。ZL202010305110.4

9. 孙周通、杨大猛:一种合成7-氨基去乙酰氧基头孢烷酸的方法。ZL202010277958.0

8. 孙周通、杨大猛:一种头孢菌素C生产菌及其制备方法与应用。ZL202010180523.4

7. 孙周通、王红月、刘贝贝:一种手性胺醇化合物的合成方法。ZL201911069262.2

6. 孙周通、张锟、梅泽龙、涂然、曲戈,一种高通量筛选酮类化合物的检测方法及其在酶筛选中的应用。CN201910763316.9

5. 孙周通、刘贝贝、曲戈、刘保艳,醇脱氢酶突变体及其在手性双芳基醇化合物合成中的应用。CN201811252380.2

4. 孙周通、赵强、刘保艳、刘贝贝、闫豪杰:一种手性3-氨基-1-丁醇的合成方法。CN201810552521.6

3. 孙周通、赵强、刘保艳、曲戈:一种手性2-氨基-1-丁醇的合成方法。CN201711181396.4

2. 孙周通、刘保艳、刘贝贝、曲戈:一种手性双芳基醇化合物的合成方法。CN201711200541.9

1. 孙周通、范文超: 酶法制备手性3-羟基四氢呋喃的工艺及醇脱氢酶突变体。专利ZL201510572955.9.

  
  

承担科研项目情况:
  

科技部合成生物学重点研发计划;中国科学院战略生物资源服务网络计划生物资源衍生库-酶库;中国科学院重点部署项目;国家自然科学基金面上项目;天津市自然科学基金面上项目;天津市杰出青年科学基金等。


获奖及荣誉:
  

2014年中国产学研合作创新成果奖;2021年优秀青年酶工程学家奖

学术兼职:

生物学杂志副主任委员;工业酶产业技术创新战略联盟副秘书长;中国生物化学与分子生物学会酶学专业分会委员;中国微生物学会酶工程专委会委员;中国生物发酵产业协会酶制剂分会理事;国际期刊Green Synthesis & CatalysisBioresources and Bioprocessing 编委,中国科协天津市科技工作者协会理事、监事长,天津化工学会常务理事。