Jian-He Xu

Photo of Biocat Lab Members and Alumini for Celebrating 15 Anniversary (2011)

Current Lab Members for Celebrating Chinese New Year of 2015

Prof. Jian-He Xu
Changjiang Professor of MOE (Ministry of Education, China), Directors of State Key Laboratory of Bioreactor Engineering and Shanghai Collaborative Innovation Center of Biomanufacturing, School of Biotechnology, ECUST.

Education
1990.09-1995.03: Ph.D. Department of Chemical Engineering, East China University of Science and Technology (ECUST), Shanghai, China.
? 1991.10-1992.08: Preliminary School for Chinese Students to Study in Japan, Changchun; 
? 1992-1994: Research Student Supported by MONBUSHO Scholarship, Kyoto University, Dept. of Synth. Chem. & Biol. Chem., Faculty of Engineering, with Prof. Atsuo Tanaka;
    1995.03: Receiving Ph. D. degree from East China University of Science and Technology, under a co-education system of China-Japan governments. 
     Ph.D. Thesis: Studies on Bioreactions Catalyzed by Lipase in Organic Solvent Systems. (Co-advisers: Prof. Ying HU of ECUST and Prof. Atsuo TANAKA of Kyoto University).
1987.09-1990.09: M.S., Department of Applied Chemistry, East China Institute of Chemical Technology, Shanghai, China.
1981.09-1987.07: B.S., Department of Chemistry, Tsinghua University, Beijing, China.

Employment: 
2012.06 – Present: Director, Shanghai Collaborative Innovation Center of Biomanufacturing.
2006.11 – Present: Director, State Key Laboratory of Bioreactor Engineering, China. 
2006.10 – Present: Vice Dean, College of Biotechnology, ECUST, Shanghai, China.
2003.08 – 2003.11: Visiting Professor, Supported by DAAD of Germany, at Institute for Chemistry and Biochemistry, University of Greifswald, with Prof. Uwe T. Bornscheuer.
2002.03 – 2006.10: Deputy Director, State Key Laboratory of Bioreactor Engineering.
2000.11 – Present: Professor, State Key Laboratory of Bioreactor Engineering, ECUST.
1999.08 – 2000.04: JSPS Postdoctoral Researcher, with Prof. Yasuhisa Asano, at Center for Biotechnology Research, Toyama Prefectural University, Toyama, Japan.
1996.11 – 2000.10: Associate Professor and Director, Laboratory of Biocatalysis, State Key Laboratory of Bioreactor Engineering (SKLBE), ECUST, Shanghai, China.
1995.04 – 1996.10: Research Associate, State Key Laboratory of Bioreactor Engineering, ECUST, Shanghai, China.

Research Interests
■ Genome Mining for and Molecular Evolution of New Enzymes;
■ Synthetic Biotechnoloy of Pharmaceutical/Natural Compounds;
■ Engineering Research and Development of Biotransformations.

Prizes and Hornors
1. Du Pont and Genecor Prize for Outstanding Contributions to China’s Enzyme Engineering, 2013.
2. Tanjiazhen Innovation Prize for Life Sciences, 2008.
3. Prize for Natural Sciences (2nd Class) by Ministry of Education, China, 2007.
4. Changjiang Professorship, Ministry of Education, China (2009). 
5. National Excellent Teachers, Ministry of Education, China (2009).
6. Special Allowance from Government awarded by State Council, China, 2006.
7. Exective Board Member, Asian Federation of Biotechnology (AFOB, 2010-2014). 
8. Editor-in-Chief, Bioresources and Bioprocessing (SpringerOpen, 2014-); Associate Editors: Applied Biochemistry and Biotechnology (2010-); Biotechnology and Bioprocess Engineering (2009-). 
9. Editorial Board Members: 1) Journal of Molecular Catalysis B: Enzymatic (2000-); 2) Applied Biochemistry and Biotechnology (2005-); 3) Process Biochemistry (2007-); 4) Chinese Journal of Catalysis (2007-); 5) Chinese Journal of Bioprocess Engineering (2008-); 6) Journal of East China University of Science and Technology (2008-). 
10. Guest Editors: Journal of Molecular Catalysis B: Enzymatic (2002, 2006 & 2009); Process Biochemistry (2008); Applied Biochemistry and Biotechnology (2008 & 2009); Biotechnology Advances (2011).
11. Conference Chairs: The 8th Sino-US Conference on Chemical Engineering (SUCE2015), Session 2 (Bioengineering and Biotechnology), Oct. 12-15, 2015, Shanghai；Asian Congress of Biotechnology (ACB-2011), May 11-15, 2011, Shanghai; International Symposium on Biocatalysis and Processing (ISBBE 2005), Oct. 16-18, 2005, Shanghai.

List of 5 Representative Papers
[1] Kong XD, Li L, Chen S, Yuan S, Zhou J*, Xu JH* (2014). Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates. Proc. Natl. Acad. Sci. U.S.A. 111: 15717–15722. 
[2] Kong XD, Ma Q, Zhou J*, Zeng BB*, Xu JH* (2014). A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-?-blocker precursors. Angew. Chem. Int. Ed. 2014, 53: 6641–6644. 
[3] Luo XJ, Kong XD, Zhao J, Chen Q, Zhou JH*, Xu JH* (2014). Switching a newly discovered lactonase into an efficient and thermostable phosphotriesterase by simple double mutations His250Ile/Ile263Trp. Biotechnol. Bioeng. 111: 1920-1930.
[4] Ma BD, Kong XD, Yu HL*, Zhang ZJ, Dou S, Xu YP, Ni Y, Xu JH* (2014). Increased catalyst productivity in α-hydroxy acids resolution by esterase mutation and substrate modification. ACS Catal. 4: 1026-1031. 
[5] Li H, Luan ZJ, Zheng GW,* Xu JH* (2015). Efficient synthesis of chiral indolines using an imine reductase from Paenibacillus lactis. Adv. Synth. Catal. 357: 1692?1696.

Recent Publications (2013-2015)

[1] Sun Z, Lonsdale R, Kong XD, Xu JH, Zhou J*, Reetz MT* (2015). Reshaping an enzyme binding pocket for enhanced and inverted stereoselectivity: Use of smallest amino acid alphabets in directed evolution. Angew. Chem. Int. Ed., 54：DOI: 10.1002/anie.201501809. 
[2] Li H, Luan ZJ, Zheng GW,* Xu JH* (2015). Efficient synthesis of chiral indolines using an imine reductase from Paenibacillus lactis. Adv. Synth. Catal., 357: 1692?1696. 
[3] Luan ZJ, Li FL, Dou S, Chen Q, Kong XD, Zhou J, Yu HL*, Xu JH* (2015). Substrate channel evolution of an esterase for the synthesis of Cilastatin. Catal. Sci. Technol. 5(5): 2622?2629.
[4] Jiao XC, Pan J*, Xu GC, Kong XD, Chen Q, Zhang ZJ, Xu JH* (2015). Efficient synthesis of statin precursor in high space-time yield by a new aldehyde-tolerant aldolase identified from Lactobacillus brevis. Catal. Sci. Technol., DOI: 10.1039/c5cy00537j
[5] Luan ZJ, Yin YC, Li AT, Yu HL*, Xu JH* (2015). Monoterpene hydroxylation with an artificial self-sufficient P450 utilizing a P450SMO reductase domain for the electron transfer. J. Mol. Catal. B: Enzym. 116: 78–82.
[6] Wu YW, Kong XD, Zhu QQ, Fan LQ*, Xu JH* (2015). Chemoenzymatic enantioconvergent hydrolysis of p-nitrostyrene oxide into (R)-p-nitrophenyl glycol by a newly cloned epoxide hydrolase VrEH2 from Vigna radiate. Catal. Commun., 58: 16?20. 
[7] Chen Q, Luan ZJ, Cheng X*, Xu JH* (2015). Molecular dynamics investigation of the substrate binding mechanism in carboxylesterase. Biochemistry, 54(9): 1841–1848. 
[8] Fan CW, Ma BD, Xu GC, Bai YP, Zhang J, Xu JH* (2015). A novel D-mandelate dehydrogenase used in three-enzyme cascade reaction for highly efficient synthesis of non-natural chiral amino acids. J. Biotechnol. 195: 67?71.
[9] Huang L, Yu HL*, Xu JH (2015). Significantly improved thermostability of a reductase CgKR1 from Candida glabrata with a key mutation at Asp 138 for enhancing bioreduction of aromatic <alpha>-keto esters. J. Biotechnol. 203: 54?61. 
[10] Cao YD, He YC, Li H, Kai GY, Xu JH and Yu HL* (2015). Efficient biosynthesis of rare natural product scopolamine using E. coli cells expressing a S14P/K97A mutant of hyoscyamine 6?-hydroxylase AaH6H. J. Biotechnol., accepted.
[11] He YC*, Tao ZC, Ding Y, Zhang DP, Wu YQ, Lu Y, Liu F, Xue YF, Wang C, Xu JH (2015). Effective biosynthesis of ethyl (R)-4-chloro-3-hydroxybutanoate by supplementation of L-glutamine, D-xylose and beta-cyclodextrin in n-butyl acetate-water media. J. Biotechnol. 203: 62?67.
[12] Liu JY, Bian HP, Tang Y, Bai YP, Xu JH* (2015). Double substituted variant of Bacillus amyloliquefaciens esterase with enhanced enantioselectivity and high activity towards 1-(3’,4’-methylenedioxyphenyl)ethyl acetate. Appl. Microbiol. Biotechnol. 99: 1701?1708. 
[13] Wang RF, Zheng MM, Cao YD, Li H, Li CX, Xu JH*, Wang ZT* (2015). Enzymatic transformation of vina-ginsenoside R7 to rare notoginsenoside ST-4 using a new recombinant glycoside hydrolase from Herpetosiphon aurantiacus. Appl. Microbiol. Biotechnol. 99(8): 3433-3442. 
[14] Zhang ZJ, Yu HL, Imanaka T, Xu JH? (2015). Efficient production of (R)-(?)-mandelic acid by isopropanol-permeabilized recombinant E. coli cells expressing Alcaligenes sp. nitrilase. Biochemical Engineering Journal, 95: 71–77.
[15] Zhang ZJ, Pan J, Ma BD, Xu JH* (2015). Efficient biocatalytic synthesis of chiral chemicals. Adv. Biochem. Eng. Biotechnol. [Epub ahead of print] 2014 Dec 24. DOI 10.1007/10_2014_291
[16] Zheng MM, Wang RF, Li CX, Xu JH* (2015). Two-step enzymatic synthesis of ursodeoxycholic acid with a new 7β-hydroxysteroid dehydrogenase from Ruminococcus torques. Process Biochemistry, 50: 598-604. 
[17] Xu GC, Yu HL*, Shang YP, Xu JH* (2015). Enantioselective bioreductive preparation of chiral halohydrins employing two newly identified stereocomplementary reductases. RSC Advances, 5: 22703-22711.
[18] Yin JG, Xu GC, Zheng GW*, Xu JH* (2015). Cloning and characterization of an enantioselective l-menthyl benzoate hydrolase from Acinetobacter sp. ECU2040. Appl. Biochem. Biotechnol., accepted.

2014
[19] Kong XD, Li L, Chen S, Yuan S, Zhou J*, Xu JH* (2014). Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates. Proc. Natl. Acad. Sci. U.S.A., 111: 15717–15722. 
[20] Kong XD, Ma Q, Zhou J*, Zeng BB*, Xu JH* (2014). A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-?-blocker precursors. Angew. Chem. Int. Ed., 2014, 53: 6641–6644. 
[21] Luo XJ, Kong XD, Zhao J, Chen Q, Zhou JH*, Xu JH* (2014). Switching a newly discovered lactonase into an efficient and thermostable phosphotriesterase by simple double mutations His250Ile/Ile263Trp. Biotechnology and Bioengineering, 111: 1920-1930.
[22] Huang L, Ma HM, Yu HL*, Xu JH* (2014). Altering the substrate specificity of a reductase CgKR1 by protein engineering for bioreduction of aromatic ?-ketoesters. Advanced Synthesis and Catalysis, 356: 1943–1948. 
[23] Zhang XY, Fan X, Qiu YJ, Li CY, Xing S, Zheng YT, Xu JH* (2014). A thermostable esterase newly identified from Sulfobacillus acidophilus: Properties and performance in phthalate esters degradation. Appl. Environ. Microbiol., 80：6870-6878. 
[24] Zhang Y, Pan J, Luan ZJ, Xu GC*, Xu JH*, Park SH (2014). Promiscuous esterase activity of a novel bacterial chloroperoxidase for highly enantioselective synthesis of a chiral cilastatin precursor. Appl Environ Microbiol, 80: 7348-7355. 
[25] Zhang Y, Ashok S, Seol E, Ainala SK, Lee SG, Madan B, Xu JH, Park S (2014). NADH-dependent lactate dehydrogenase from Alcaligenes eutrophus H16 reduces 2-oxoadipate to 2-hydroxyadipate. Biotechnol Bioprocess Eng, 19(6): 1048-1057.
[26] Gong Y, Xu GC, Li CX*, Zheng GW, Xu JH* (2014). A thermostable variant of Bacillus subtilis esterase: characterization and application for resolving dl-menthyl acetate. J. Mol. Catal. B: Enzym. 109: 1-8.
[27] Chen RJ, Zheng GW*, Ni Y, Zeng BB, Xu JH* (2014). Efficient synthesis of a ε-hydroxy ester in a space-time yield of 1580 g L-1 d-1 by a newly identified reductase RhCR. Tetrahedron: Asymmetry, 25: 1501–1504.
[28] Li SX*, Ma Q, Lin K, Wu JJ, Wu YX, Xu JH* (2014). Essential role of Gly33 in a novel organic solvent-tolerant lipase from Serratia marcescens ECU1010 as determined by site-directed mutagenesis. Appl. Biochem. Biotechnol. 172: 2945-2954. 
[29] He YC, Tao ZC, Zhang X, Yang ZX, Xu JH (2014). Highly efficient synthesis of ethyl (S)-4-chloro-3-hydroxybutanoate and its derivatives by a robust NADH-dependent reductase from E. coli CCZU-K14. Bioresour. Technol. 161: 461-464. 
[30] Liu XY, Li CX, Luo XJ, Lai QL, Xu JH* (2014). Burkholderia jiangsuensis sp. nov., a methyl parathion (MP)-degrading bacterium, isolated from MP-contaminated soil. Int. J. Syst. Evol. Microbiol. 64: 3247-3253. 
[31] Liu XY, Luo XJ, Li CX, Lai QL, Xu JH* (2014). Draft genome sequence of Burkholderia sp. strain MP-1, a methyl parathion (MP)-degrading bacterium from MP-contaminated soil. Genome Announc. 2(3): e00344-14.  
[32] Du FL, Yu HL, Xu JH, Li CX* (2014). Enhanced limonene production by optimizing the expression of limonene biosynthesis and MEP pathway genes in E. coli Bioresour. Bioprocess. 2014, 1: 10.
[33] Pan J, Dang ND, Zheng GW*, Cheng B, Ye Q, Xu JH* (2014). Efficient production of l-menthol in a two-phase system with SDS using an immobilized Bacillus subtilis esterase. Bioresour. Bioprocess. 2014, 1: 12.  
[34] Pan J, Zheng GW, Ye Q, Xu JH* (2014). Optimization and scale-up of bioreduction process for cost-effective production of (S)-4-chloro-3-hydroxybutanoate. Org. Process Res. Dev., 18: 739-743.
[35] Qian XL, Pan J, Shen ND, Ju X, Zhang J* and Xu JH* (2014). Efficient production of ethyl (R)-2-hydroxy-4-phenylbutyrate using an economically competitive reductase expressed in Pichia pastoris. Biochemical Engineering Journal, 91: 72-77.
[36] Zhang ZJ, Pan J, Li CX, Yu HL, Ju X, Xu JH* (2014). Efficient production of (R)-(-)-mandelic acid using glutaraldehyde cross-linked Escherichia coli cells expressing Alcaligenes sp. nitrilase. Bioprocess Biosystems Eng. 37: 1241–1248.  
[37] Liu JY, Zheng GW*, Imanaka T, and Xu JH* (2014). Stepwise and combinatorial optimization of enantioselectivity for asymmetric hydrolysis of 1-(3’,4’-methylene dioxyphenyl)ethyl acetate  using a cold-adapted Bacillus amyloliquefaciens esterase. Biotechnol. Bioprocess Eng. 19: 442-448.
[38] Ni Y, Hagedoorn PL, Xu JH, Arends IWC E, Hollmann F* (2014). Pyrococcus furiosus-mediated reduction of conjugated carboxylic acids: towards using syngas as reductant. J. Mol. Catal. B: Enzymatic, 103: 52–55. 
[39] Dou S, Kong XD, Ma BD, Chen Q, Zhang J, Zhou JH*, Xu JH* (2014). Crystal structures of Pseudomonas putida esterase reveal the functional role of residues 187 and 287 in substrate binding and chiral recognition. Biochem. Biophys. Res. Comm. 446: 1145–1150. 
[40] Yin YC, Yu HL*, Luan ZJ, Li RJ, Ouyang PF, Liu J, Xu JH (2014). Unusually broad substrate profile of a self-sufficient cytochrome P450 monooxygenase CYP116B4 mined from Labrenzia aggregate. ChemBioChem, 15: 2443-2449. 
[41] Xu YP, Yu HL*, Guan YH, Ni Y, Ma BD, Xu JH* (2014). Significantly improved methyl o-chlorobenzoylformate bioreduction by stabilizing aldo-keto reductase YtbE with additives chosen based on inactivation mechanism elucidation. J. Mol. Catal. B: Enzymatic, 104: 108–114. 
[42] Li J, Pan J,  Zhang J*, Xu JH* (2014). Stereoselective synthesis of L-tert-leucine by a newly cloned leucine dehydrogenase from Exiguobacterium sibiricum. J. Mol. Catal. B: Enzymatic, 105: 11–17.  
[43] Ma BD, Kong XD, Yu HL*, Zhang ZJ, Dou S, Xu YP, Ni Y, Xu JH* (2014). Increased catalyst productivity in α-hydroxy acids resolution by esterase mutation and substrate modification.  ACS Catal., 4: 1026-1031. 
[44] Nguyen-Tran HH, Zheng GW*, Qian XH and Xu JH* (2014). Highly selective and controllable synthesis of arylhydroxylamines by the reduction of nitroarenes with an electron-withdrawing group using a new nitroreductase BaNTR1. Chem. Comm. 50: 2861?2864.
[45] Ni Y, Yu HL, Lin GQ, Xu JH* (2014). A new ene reductase from Clavispora lusitaniae for asymmetric reduction of activated alkenes. Enzyme Microb. Technol. 56: 40–45. 
[46] Zhu QQ, He WH, Kong XD, Fan LQ*, Zhao J, Li SX, Xu JH* (2014). Heterologous overexpression of Vigna radiata epoxide hydrolase in Escherichia coli and its catalytic performance in enantioconvergent hydrolysis of p-nitrostyrene oxide into (R)-p-nitrophenyl glycol. Appl. Microbiol. Biotechnol. 98: 207?218. 
[47] Zhou WJ, Ni Y, Zhu ZR, Zheng GW*, Chen HH, Zhu ZR and Xu JH* (2014). Enzymatic resolution of a chiral chlorohydrin precursor for (R)-α-lipoic acid synthesis via lipase catalyzed enantioselective transacylation with vinyl acetate. J. Mol. Catal. B: Enzymatic, 99: 102?107.
[48] Hu K, Li CX*, Pan J, Ni Y, Zhang XY, Xu JH* (2014). Performance of a new thermostable mannanase in breaking guar-based fracturing fluids at high temperatures with little premature degradation. Appl. Biochem. Biotechnol., 172(3): 1215-1226.
[49] Yan Ni, Hui-Lei Yu and Jian-He Xu (2014). Solvent effects in bioreductions. Chapter 9, in: Synthetic Methods for Biologically Active Molecules, ed. E. Brenna, Wiley-VCH, 2014, Weinheim.

2013
[50] Zhang WX, Xu GC, Huang L, Pan J, Yu HL*, Xu JH* (2013). Highly efficient synthesis of (R)-3-quinuclidinol in a space-time yield of 916 g L-1 d-1 using a new bacterial reductase ArQR. Org. Lett. 15(19): 4917?4919.
[51] Xu GC, Yu HL*, Zhang ZJ, Xu JH* (2013). Stereocomplementary bioreduction of β-ketonitrile without  ethylated  byproduct. Org. Lett. 15(21): 5408–5411. 
[52] Ma BD, Yu HL*, Pan J, Liu JY, Ju X, Xu JH* (2013). A thermostable and organic-solvent tolerant esterase from Pseudomonas sp. ECU1011: Catalytic properties and performance in kinetic resolution of α-hydroxy acids. Bioresour. Technol. 133: 354?360. 
[53] Shi RR, Li ZM, Ye Q, Xu JH, Liu Y (2013). Heterologous expression and characterization of a novel thermo-halotolerant endoglucanase Cel5H from Dictyoglomus thermophilum. Bioresour. Technol. 142: 338–344.  
[54] He YC*, Xia DQ, Ma CL, Gong L, Gong T, Wu MX, Zhang Y, Tang YJ, Xu JH, Liu YY* (2013). Enzymatic saccharification of sugarcane bagasse by N-methylmorpholine- N-oxide-tolerant cellulase from a newly isolated Galactomyces sp. CCZU11-1. Bioresour. Technol. 135: 18–22.  
[55] Zhou DJ, Pan J*, Yu HL, Zheng GW, Xu JH* (2013). Target-oriented discovery of a new esterase-producing strain Enterobacter sp. ECU1107 for whole cell-catalyzed production of (2S,3R)-3-phenylglycidate as a chiral synthon of Taxol. Appl. Microbiol. Biotechnol. 97(14): 6293-6300.  
[56] Liu CH, Pan J, Ye Q, Xu JH* (2013). Enzymatic production of Cilastatin intermediate via highly enantioselective hydrolysis of methyl (±)-2,2-dimethylcyclopropane carboxylate using newly isolated Rhodococcus sp. ECU1013. Appl. Microbiol. Biotechnol. 97: 7659–7667.  
[57] He YC*, Ma CL, Zhang X, Li L, Xu JH, Wu MX (2013). Highly enantioselective oxidation of racemic phenyl-1,2-ethanediol to optically pure (R)-(-)-mandelic acid by a newly isolated Brevibacterium lutescens CCZU12-1. Appl. Microbiol. Biotechnol. 97: 7185–7194.  
[58] Liu JY, Zheng GW*, Li CX, Yu HL, Pan J, Xu JH* (2013). Multi-substrate fingerprinting of esterolytic enzymes with a group of acetylated alcohols and statistic analysis of substrate spectrum. J. Mol. Catal. B: Enzymatic 89: 41–47. 
[59] Zheng GW, Liu XY, Zhang ZJ, Tian P*, Lin GQ, Xu JH* (2013). Separation of enantiopure m-substituted 1-phenylethanols in high space-time yield using Bacillus subtilis esterase. RSC Adv. 3: 20446-20449.  
[60] Zhang YHP, Xu JH, Zhong JJ (2013). A new high-energy density hydrogen carrier — carbohydrate — might be better than methanol. Int. J. Energy Res. 37: 769–779.
[61] Ngo-Thi MT, Yin JG, Pan J, Zheng GW*, Xu JH* (2013). Enantioselective hydrolysis of dl-menthyl benzoate by cell-free extract of newly isolated Acinetobacter sp. ECU2040. Appl. Biochem. Biotechnol., 170: 1974–1981. 
[62] Ouyang LM*, Liu JY, Qiao M, Xu JH* (2013). Isolation and biochemical characterization of two novel metagenome-derived esterases. Appl. Biochem. Biotechnol. 169: 15?28.  
[63] Li SX*, Lin K, Pang HY, Wu YX, Xu JH (2013). Production, characterization, and application of an organic solvent-tolerant lipase present in active inclusion bodies. Appl. Biochem. Biotechnol. 169: 612–623.
[64] Xu GC, Yu HL*, Xu JH* (2013). Facile access to chiral alcohols with pharmaceutical relevance using a ketoreductase newly mined from Pichia guilliermondii. Chin. J. Chem. 31: 349?354. 
[65] Naqvi SHA, Dahot MU, Khan MY, Xu J, Rafiq M (2013). Usage of sugar cane bagasse as an energy source for the production of lipase by Aspergillus fumigatus. Pakist. J. Botany, 45: 279–284.

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(Updtaed on Aug. 10, 2015)