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酶定向进化与生物催化 酶分子工程是实现微生物合成生物学中酶新功能新反应设计与应用的重要手段；对酶催化口袋的再设计与新反应催化机制的研究是新酶新反应设计中的重要研究内容，是实现医药中间体、天然产物等微生物合成的再设计与产物手性控制的理论与应用基础。课题组围绕酶定向设计方法的研究与酶底物结合口袋的再设计与催化机制的解析，针对天然生物酶存在诸如催化效率低、立体选择/区域选择性较差、底物谱窄、热稳定性差及催化机制不清楚等问题。基于生物信息学与计算设计进行新型工业用酶挖掘设计与再设计，结合分子定向进化改造及计算机(in silico)辅助设计与筛选；开展重要工业医药用酶，如：环氧水解酶、醇脱氢酶、P450单加氧酶、氨基酸脱氢酶、糖基转移酶、脂肪酶及羧酸还原酶等的研究；开发酶的精准设计与定向进化方法，基于晶体结构与计算解析新反应催化机制，应用于酶催化重要医药中间体及天然产物的高效微生物催化合成。
代表论著：
论文
2020
33. Chen, J#, Fan, F#, Qu, G#, Tang, J, Xi, Y, Bi, C, Sun Z*, and 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
32. 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.
31. 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
30. 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.
29. 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.
28. 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.
27. 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.
26. 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.
25. Sun Z*, Liu Q, Qu G, Feng Y*, and 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.
24. Qu G#, Fu M#, Zhao L, Liu B, Liu P, Fan W, Ma J, and Sun Z*. Computational Insights into the Catalytic Mechanism of Bacterial Carboxylic Acid Reductase. J. Chem. Inf. Model., 2019, 59, 832-841.
23. Dai Z#, Liu Y#, Sun Z#, Wang D, Qu G, Ma X, Fan F, Zhang L, Li S, and 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.
22. 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.
21. Sun Z, and 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.
20. Qu G, Sun Z*, and Reetz MT*. Iterative Saturation Mutagenesis for Semi-rational Enzyme Designin “Protein engineering”, Wiley 2019, Book chapter(in production)
2018
19. Li A, Sun Z, and 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, and 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*, and 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*, and 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. 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(Chin. J. Biotech.), 2018, 34(1): 1-11. 特邀综述。
14. Li A, Acevedo-Rocha CG, Sun Z, Cox T, Xu J, and 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*, and 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* and 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#, and 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，and 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#, and 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, and 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*, and 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*, and 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, and 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*, and 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, and 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*, and 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, and Yang S*. Metabolic engineering of the L-phenylalanine pathway in Escherichia coli for the production of S- or R-mandelic acid. Microbial Cell Factories, 2011, 10:71. “highly accessed”
申请及授权发明专利
[11]. 孙周通、王红月、刘贝贝：一种手性胺醇化合物的合成方法。CN201911069262.2
[10]. 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
[9]. 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
[8]. 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
[7]. 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
[6]. 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
[5]. 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CN201510572955.9.
[4].杨晟、陶荣盛、朱傅赟、赵丽丽、蒋宇、杨俊杰、孙周通、沈正权、黄鹤、孙梁栋、董枫、刘映淼：用于生产L-2-氨基丁酸的载体、工程菌株及方法。专利授权号：ZL201210015308.4. 授权日期：2015-11-18.
[3]. 孙周通、刘映淼、孙兵兵、王祎、吴辉、杨俊杰、黄鹤、杨晟、李成玉、于丽、王德辉：L-色氨酸基因工程菌，其构建方法以及使用其发酵生产L-色氨酸的方法。专利授权号：ZL201010598350.4. 授权日期：2014-8-27.
[2]. 杨晟、孙周通、姜卫红：手性单体扁桃酸的获得方法. 专利授权号：ZL201010570887.X. 授权日期：2014-7-16.
[1]. 杨晟、黄鹤、孙周通：一种二氢吡啶二羧酸合成酶。专利授权号：ZL201010117533.X. 授权日期：2013-10-9.
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