许建和
主要研究立体选择性生物催化技术及其在手性合成中的应用。
个性化签名
- 姓名:许建和
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学术头衔:
博士生导师
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学科领域:
生物化学工程
- 研究兴趣:主要研究立体选择性生物催化技术及其在手性合成中的应用。
许建和,华东理工大学生物工程学院教授、博士生导师,国际核心期刊Journal of Molecular Catalysis B: Enzymatic编委。1987年毕业于清华大学,留日博士、博士后。1995年起受聘于生物反应器工程国家重点实验室,曾任学术秘书、支部书记,现任重点实验室副主任、生物催化研究室主任,北京市生物加工过程重点实验室学术委员。教育部优秀青年教师、上海市青年科技启明星;获日本明治乳业生命科学奖和德国学术交流协会(DAAD)研究访问奖。主要研究立体选择性生物催化技术及其在手性合成中的应用,并创造性地提出了生物催化法破解手性难题的两个重要思路:一是筛选,二是改造。主要成果包括:1)非水相酶催化的对映选择性酯化及其在手性醇、酸、酯制备中的应用;2) 酶的立体选择性调控方法及其在手性2-芳基丙酸拆分中的应用;3)立体专一性微生物酶的筛选方法及在各种光学活性产品合成中的应用。主持过多项手性生物催化方面的重要研究课题,包括4项国家自然科学基金、1项国家“九五”攻关专题和1项国际合作研究项目;参加国家自然科学基金重大基金“手性及手性药物研究中的若干科学问题研究”(子课题:与手性药物有关的手性砌块的生物催化合成研究)和国家重大基础研究计划(973) 项目”生物催化与生物转化的若干基础问题研究”(子课题: 非水相不对称生物催化)。已在国内外核心期刊发表论文90多篇, 被SCI收录40多篇,EI收录20篇,他人引用110多次;受邀作国际和国内大会或特邀报告10次。申报5项发明专利,其中3项已获专利授权,1项获上海市优秀职务发明奖,部分菌种、样品和工艺已经或正在向有关企业转移和推广应用。
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816
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成果数
20
许建和, Jian-He Xu, * Yasuo Kato, Yasuhisa Asano
BIOTECHNOLOGY AND BIOENGINEERING, VOL. 73, NO.6, JUNE 20, 2001, 493~499,-0001,():
-1年11月30日
Optically active (R)-a-monobenzoyl glycerol (MBG) was synthesized by Candida antarctica lipase B (CHIRAZYMET L-2) catalyzed asymmetric esterification of glycerol with benzoic anhydride in organic solvents. Various conditions, such as the type and composition of the organic solvent, water content of the system, reaction temperature, and concentrations of the substrates were systematically examined and optimized in screw-capped test tubes with respect to both the reaction rate and the enzyme selectivity. 1,4-Dioxane was found to be the best solvent and no additional water was needed for the system. The optimum temperature was around 30℃, while the most suitable substrate concentrations were 100mM each for glycerol and benzoic anhydride, respectively. However, when excessive anhydride (e.g., 200mM) was used, the produced MBG could be further transformed into 1,3-dibenzoyl glycerol (DBG) by the same enzyme with a priority to (S)-MBG, resulting in a significant improvement of the product optical purity from ca. 50-70% e.e. Under optimal conditions (100mM glycerol, 100-200mM benzoic anhydride, dioxane, 25-30℃), the enzymatic synthesis of (R)-MBG was successfully operated in a packed-bed reactor for about 1 week, with an average productivity of 0.79g MBG/day/g biocatalyst in the case of continuous operation and 0.94g MBG/day/g biocatalyst in the case of semicontinuous operation. After refinement and preferential crystallization of the crude product, (R)-MBG could be obtained in an almost optically pure form (>98% e.e.).
Candida antarctica lipase B, asymmetric esterification, (, R), -a-monobenzoyl glycerol, benzoic anhydride, monoglyceride, packed bed reactor
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【期刊论文】Significant enhancement of lipase enantioselectivity toward (S)-Ketoprofen ester at pH 2
许建和, You-Yan Liu, Jian-He Xu, Qiu-Ge Xu & YingHu
Biotechnology Letters 21: 143~146, 1999.,-0001,():
-1年11月30日
The optimal activity of a Candida rugosa lipase (Lipase OF) for hydrolysis of 2-chloroethyl ester of Ketoprofen [2-(3-benzoyphenyl) propionic acid] was at pH 4.0, while the best enantioselectivity (E) was at pH 2.2 where the enzyme was still 60% active and stable.
(, S), -Ketoprofen,, Candida rugosa lipase,, pH effect,, activity,, enantioselectivity
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许建和, P.-F. Gong
Appl Microbiol Biotechnol (2002) 58: 728~734,-0001,():
-1年11月30日
The yeast strain CGMCC 0573 was identified as Citeromyces matriensis and shown to be capable of enantioselectively hydrolyzing ethyl ester of (R)-Ketoprofen (2-(3-benzoylphenyl)propionic acid). The strain was isolated for the first time from soil samples through a new and efficient screening procedure in which the probability of obtaining active strains was greatly increased by using ethanol and Tween-80 alternatively as additives during the enrichment culture. Studies of the culture conditions and catalytic performance of Citeromyces matriensis CGMCC 0573 showed that the enzyme occurs constitutively in the cells and its production is enhanced by feeding with Tween-80 during the early period of cultivation. Yeast extract was found to be beneficial both for growth and for esterase production. The optimal temperature and pH for the bioconversion were 40℃ and pH 8.0, respectively. Biotransformation using resting cells cultured in a flask with baffles and magnetic stirring and in the presence of 50mM substrate resulted in the production of (R)-ketoprofen at 93% ee (enantiomeric excess) and at 42.6% conversion.
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许建和, Li Gao
Ind Microbiol Biotechnol (2004) 31: 525~530,-0001,():
-1年11月30日
Lipase production and cell growth of Serratia marcescens ECU1010 were optimized in shake flasks, with lipase production being enhanced 9.5-fold (4,780 U/l) compared with the initial activity (500 U/l). Optimal carbon and nitrogen sources were Tween-80 and peptone, and the optimal ratio of Tween-80 to peptone was 1:3. The optimized cultivation conditions were 25[1]C and pH 6.5. Lipase activity, particularly specific activity, could be improved by decreasing the cultivation temperature from 35 to 25[1]C. Enzyme stability was significantly improved by simple immobilization with synthetic adsorption resin no. 8244. After five reaction cycles, enzyme activity decreased only very slightly, while enantioselectivity of the preparation remained constant, and the ees (enantiomeric excess of the remaining substrate) achieved in all cases was higher than 97%. The resin-8244-lipase preparation can be used for efficient enantioselective hydrolysis of trans-3-(4
Serratia marcescens ECU1010
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【期刊论文】Asymmetric reduction of aryl ketones with a new isolate Rhodotorula sp. AS2.2241
许建和, Ye Ni, Jian-He Xu*
Journal of Molecular Catalysis B: Enzymatic 18(2002)233~241,-0001,():
-1年11月30日
A yeast strain, Rhodotorula sp. AS2.2241, capable of reducing acetophenone and -bromoacetophenone with high stereoselectivity, was isolated from soil samples through a novel screening procedure in which acetophenone was supplied in vapor state as the sole carbon and energy source. The biosynthesis of the ketone reductase in the yeast cells reached a maximum of 41.0 U/l at 20h of cultivation. The reductase isolated from the Rhodotorula sp. cells was partially purified by 52.6-fold through a single column chromatography of DEAE-cellulose. The catalytic performance of the partially purified reductase was examined, and the highest activitywas observed at pH 6.5 and 50 ◦C. The short-chain alkyl aldehydes such as acetaldehyde and those aldehydes or ketones with a benzoyl group were found to be good substrates for the reductase. In the preparative bioreductions of 50mM acetophenone and 2mM -bromoacetophenone using resting cells of Rhodotorula sp. AS2.2241, (S)-(−)-1-phenylethanol (>99.5% enantiomeric excess (e.e.), 34.7% yield) and (R)-(−)-2-bromo-1-phenylethanol (>99.9% e.e., 19.9% yield) were obtained, respectively.
Acetophenone, a-Bromoacetophenone, Asymmetric reduction, Ketone reductase, Aldehyde reductase, Rhodotorula sp.,
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许建和, Yan-Fa Tang a, Jian-He Xua, *, Qin Ye a, Birgit Schulze b
Journal of Molecular Catalysis B: Enzymatic 13(2001)61~68,-0001,():
-1年11月30日
A bacterial strain (ECU1001) capable of utilizing phenyl glycidyl ether as sole carbon source and energy source was isolated from soil samples through two steps of screening and was identified as a Bacillus megaterium. The epoxide hydrolase from Bacillus megaterium ECU1001 was biosynthesized in parallel with cell growth and a maximum activity of 31.0 U/l was reached after 30h of culture when the biomass (DCW) was 9.1g/l. A temperature of 35◦C and pH 8.0 were optimal for the bioconversion. The lyophilized whole cells of Bacillus megaterium ECU1001 could preferentially hydrolyze the (R)-enantiomer of phenyl glycidyl ether, yeilding (S)-epoxide and (R)-diol with high enantioselectivity (E=47.8). The (S)-enantiomer of the epoxide remained in the reaction mixture with >99.5% ee (enantiomeric excess) at a conversion of 55.9%. The substrate concentration could be increased up to 60mM without affecting the ee and (S)-phenyl glycidyl ether could be obtained with an optical purity of 100% ee and 25.6% yield. Therefore, the method is potentially useful for the preparative resolution of epoxides.
Phenyl glycidyl ether, Bacillus megaterium, Epoxide hydrolase, Kinetic resolution, Enantioselective hydrolysis
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许建和, Yi Xu, Jian-He Xu*, Jiang Pan, Liang Zhao, Si-Liang Zhang
Journal of Molecular Catalysis B: Enzymatic 27(2004)155~159,-0001,():
-1年11月30日
Biocatalytic resolution of 3-(2'-nitrophenoxy)propylene oxide (1a), 3-(3'-nitrophenoxy)propylene oxide (1b) and 3-(4'-nitrophenoxy)propylene oxide (1c) were exploited by using lyophilized cells of yeast Trichosporon loubierii ECU1040 with epoxide hydrolase (EH) activity, which preferentially hydrolyzes (S)-enantiomers of the epoxides (1a-c), yielding (S)-diols and (R)-epoxides. The activity increased as the nitro group in the phenyl ring was shifted from 4'-position (1c) to 2'-position (1a). When the substrate concentration of 1a was increased from 10 to 80mM, the E-value increased at first, until reaching a peak at 40mM, and then decreased at higher concentrations (>40mM). The optically active epoxide (R)-1a was prepared at gram-scale (97% ee, 41% yield). Furthermore, a simple method was developed to predict the enantiomeric excess of substrate (ees) at any time of the whole reaction course based on the ees value determined at a certain reaction time at a relatively lower substrate concentration. This will be helpful for terminating the reaction at a proper time to get both higher optical purity and higher yield of the remaining epoxides.
Nitro-substituted phenoxypropylene oxide, Trichosporon loubierii, Epoxide hydrolase, Kinetic resolution, Theoretical prediction, Enantioselective hydrolysis
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许建和, Ai-Min Tong a, Jian-He Xu a, *, Wen-Ya Lu b, Guo-Qiang Lin b
Journal of Molecular Catalysis B: Enzymatic 32(2005)83~88,-0001,():
-1年11月30日
A monophasic organic-water system for efficient enzymatic synthesis ofβ-d-glucopyranoside by reverse hydrolysis was constructed and optimized. p-Nitrobenzyl alcohol (pNBA), selected as a model substrate alcohol, was readily glucosylated with d-glucose through reverse hydrolysis using almond β-d-glucosidase in a monophasic aqueous-organic medium, producing a new glucoside, p-nitrobenzylβ-d-glucopyranoside (pNBG). The effects of different buffers, organic solvents and water contents were investigated. Buffer type and Ph affected the initial reaction rate but had little effect on the final yields. The ratio of organic solvent to water plays a crucial role in shifting the reaction equilibrium toward synthesis, but a minimum amount of water is necessary to maintain the enzyme activity. Dioxane, which was previously known as an unsuitable solvent forβ-d-glucosidase-catalyzed reactions, was found to be the most appropriate solvent for this synthetic procedure. The reaction equilibrium and enzyme stability in the reaction medium were also investigated. Under the optimal reaction conditions, i.e. 90% dioxane (v/v) + 10% buffer (Na2HPO4–KH2PO4, 70mM, pH 6.0) with alcohol-to-glucose molar ratio of 9:1, p-nitrobenzylβ-d-glucopyranoside was produced with a maximum yield (13.3%).
Reversed hydrolysis, β-d-Glucopyranoside, Almond β-d-glucosidase, Organic medium, Dioxane-water system
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许建和, Ya Chen, Jian-He Xu*, Jiang Pan, Yi Xu, Ji-Bin Shi
Journal of Molecular Catalysis B: Enzymatic 30(2004)203~208,-0001,():
-1年11月30日
Kinetic resolution of a chiral alcohol, 4-hydroxy-3-methyl-2-(2[1]-propenyl)-2-cyclopentenone (HMPC), a key intermediate for the production of prallethrin insecticides, was successfully carried out by enantioselective hydrolysis of (RS)-HMPC acetate using calcium alginate gel-entrapped cells of a newly isolated esterase-producing bacterium Acinetobacter sp. CGMCC 0789. When the effect of different cosolvents was investigated, it was found that isopropanol could markedly enhance the activity and enantioselectivity of the immobilized cells. The optimum concentration of isopropanol was 10% (v/v) where immobilized cells still showed good operational stability. After 10 cycles of reaction, no significant decrease in the enzyme activity was observed. The catalytic specificity constants (Vmax/Km) for both enantiomers of the substrate were determined with partially purified enzyme, giving 0.0184 and 0.671 h−1for the (S)- and (R)-ester, respectively.
Acinetobacter sp., esterase, Enantioselectivity, Enzymatic resolution, 4-Hydroxy-3-methyl-2-(, 2[1]-propenyl), -2-cyclopentenone, Immobilized cells, Isopropanol
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许建和, Jing-Hua Qian, Jian-He Xu*
Journal of Molecular Catalysis B: Enzymatic 27(2004)227~232,-0001,():
-1年11月30日
A highly enantioselective (R)-ester hydrolase was partially purified from a newly isolated bacterium, Acinetobacter sp. CGMCC 0789, whose resting cells exhibited a highly enantioselective activity toward the acetate of (4R)-hydroxy-3-methyl-2-(2-propynyl)- cyclopent-2-enone (R-HMPC). The optimum pH and temperature of the partially purified enzyme were 8.0 and 60℃, respectively. The enantioselectivity of the crude enzyme was increased by 1.2-fold from 16 to 20 when the reaction temperature was raised from 30 to 60℃. The activity of the crude enzyme was enhanced by 4.1-fold and the enantioselectivity (E-value) was markedly enhanced by 4.3-fold from 16 to 68 upon addition of a cationic detergent, benzethonium chloride [(diisobutyl phenoxyethoxyethyl) dimethyl benzylammoniom chloride]. The hydrolysis of 52mM (R,S)-HMPC acetate to (R)-HMPC was completed within 8 h, with optical purity of 91.4% eep and conversion of 49%.
Acinetobacter sp., , Esterase, Enantioselectivity, Allethrin, Enzymatic resolution
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