SUN Zhoutong----Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences

SUN Zhoutong, Ph.D.

Principle Investigator, TIB, Tianjin, China

Tel: 86-22-84861981

E-mail: sunzht@tib.cas.cn

Education

2005-2011 Ph.D. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

2003-2005 B.S. Department of Bioengineering, School of Life Sciences, Henan University, Henan, China

2000-2003 College of Biology Engineering, Henan University of Animal Husbandry and Economy, Henan, China

Professional Experience

2016-now Principle Investigator, Full Professor, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China

2013-2016 Postdoctoral Research Fellow in Manfred T. Reetz group, Department of Chemistry, Max-Planck-Institute for Coal Research and Philipps-University Marburg, Marburg, Germany

2012-2013 Postdoctoral Research Fellow in Susanna Su Jan Leong group, Division of Chemical and Biomolecular Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore

2012 Research associate/project manager, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Research and Development Center of Industrial Biotechnology, Shanghai, China

Research Interests

The research in our group is mainly focused on discovery, design and engineering of biocatalyst, cascade reaction design and pathway engineering, our research interests include:

a) genome mining of new types of biocatalyst by bioinformatics analysis;

b) protein engineering and directed evolution of important industrial enzymes to improve or achieve new functions;

c) rational design and in silico directed evolution of new biocatalysts;

d) methodology development in directed evolution.

Selected Publications

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, 38(04),1518-1526.

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. 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, doi.org/10.1016/j.jbiotec.2019.09.006.

26. Qu G^#, Li A^#, Acevedo-Rocha CG^#, Sun Z*, and Reetz MT*. The Crucial Role of Methodology Development in Directed Evolution of Selective Enzymes. Angew. Chem. Int. Ed., 2019, DOI: 10.1002/anie.201901491.

25. Li A^#, Qu G^#, Sun Z*, and 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.

24. Liu B^#, Qu G^#, Li J, Fan W, Ma JA, Xu Y, Nie Y*, and 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.

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

22. 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.

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

20. 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.

19. 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.

2018

18. 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.

17. 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.

16. 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.

15. 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.

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.

10．Li A, Ilie A, Sun Z, Lonsdale R, Xu JH，Reetz 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.

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.

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.