Molecular Catalysis
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2025
·
IF 4.9
Jiali Chen,Chen Huang,Yuqing Zhang,Liya Zhou,Li Ma,Lihui Wang,Yanjun Jiang,Yunting Liu
The conversion of racemic alcohols to enantiopure alcohols and amines is of significant importance yet presents considerable challenges. Herein, we achieved this goal by developing continuous-flow chemoenzymatic systems. In chemical module, a ruthenium (II)-N-heterocyclic carbene (Ru-NHC) catalyst immobilized on dendritic organosilica nanoparticle (DON) was prepared, which exhibited high activity and selectivity in the dehydrogenative oxidation of racemic alcohols to ketones. In enzymatic module, a ketoreductase and an amine dehydrogenase were individually co-immobilized with a cofactor-regenerating enzyme (glucose dehydrogenase) on DON for the enantioselective conversion of ketones to chiral alcohols and amines, respectively. The integration of the two modules in continuous-flow systems enabled the efficient chemoenzymatic deracemization and asymmetric amination of racemic alcohols (9 examples) with the maximum space-time yields of 6.8 and 5.8 g L -1 h -1 , respectively, underscoring the practical utility of the continuous-flow chemoenzymatic systems.
研究领域:
生物化学
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有机化学
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合成生物学
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DOI
高影响因子
Molecular Catalysis
·
2022
·
IF 5.089
Ying Zhang,Zhi-Wen Duan,Han-Yu Liu,Feng Qian,Pu Wang
Microbial whole-cell catalysis has been a popular method for chiral alcohols preparation. In this study, Cyberlindnera saturnus ZJPH1807 was successfully employed as a biocatalyst to reduce 2-chloro-1-(2,4-dichlorophenyl)ethanone (CPE) to ( R )-2-chloro-1-(2,4-dichlorophenyl)ethanol (( R )-CPEO), a key chiral intermediate of antifungal drug miconazole. In order to further improve the bioprocess yield, natural deep eutectic solvent and cyclodextrin were introduced into the reaction system as additives. It was found that carnitine/trehalose (C/Tre, 1:1 mol/mol) could increase the permeability of cell membrane appropriately and improve the mass transfer rate. And the addition of methyl-β-cyclodextrin (MCD) could improve the solubility of CPE in buffer solution, simultaneously promoting cofactor recycling. Furthermore, MCD and C/Tre exerted a synergistic effect on the acceleration of CPE bioreduction, producing 91.0% yield in 1.5 h at 35.8 mM CPE in a C/Tre-MCD-containing system, with a 12.4-fold increase in productivity compared to neat buffer solution only. When the substrate loading was increased to 67.1 mM, the yield could also achieve 84.2%. The established bioreduction process was also feasible at 100 mL preparation scale with a 88.5% ( R )-CPEO yield. The integration of C/Tre and MCD can significantly improve catalytic efficiency for hydrophobic substrates and be applied in biocatalysis.
研究领域:
生物化学
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微生物学
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制药工程
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DOI
高影响因子
CHINESE JOURNAL OF CHEMISTRY
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2015
·Vol. 33
·期 5
·578-582
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IF 1.578
Minting Liang,Xiaofeng Xia,Xiang Liu,Hexing Li
In the presence of the inexpensive and non-toxic polymethylhydrosiloxane, the combination of copper(II) acetate and a chiral diphosphine displayed high catalytic efficiency in the asymmetric hydrosilylation of a series of aromatic ketones in air atmosphere and at room temperature. ( R )-1-Arylethanols were obtained with up to 99% yield and 93% enantiomeric excess. Meanwhile, the electron effect and steric hindrance of substituents on the aromatic ring had an interesting influence on both the yields and enantioselectivities. Furthermore, a possible mechanism was presented to explain the influence of some key factors on the reaction.
研究领域:
有机化学
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催化化学
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产品关联
DOI
高影响因子
ORGANIC PROCESS RESEARCH & DEVELOPMENT
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2014
·
IF 2.549
Liang Xu,Zhi-Hong Huang,Christian A. Sandoval,Lian-Quan Gu,Zhi-Shu Huang
A novel efficient asymmetric hydrogenation (AH) process was developed for the preparation of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethanol (3), using a catalyst Ru/(4R,5R)-(+)-4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxoane-(R,R-Diop)-2R-(α-methylmethanamine)-4,7-dimethyl-1H-benzo[d]imidazole (R-D-Me-BIMAH) in toluene in the presence of potassium t-butoxide. Various hydrogenation parameters, such as ligand, solvent, and substrate-to-catalyst (S/C) ratio, were investigated. The hydrogenation was carried out for four times on a 5 kg scale at 30 atm and 25 °C with S/C of 20 000 with an enantiomeric excess of >89%.
研究领域:
有机化学
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催化化学
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DOI
高影响因子
MOLECULES
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2016
·Vol. 21
·期 11
·1466
·
IF 2.465
Shengming Xie,Junhui Zhang,Nan Fu,Bangjin Wang,Cong Hu,Liming Yuan
Molecular organic cage compounds have attracted considerable attention due to their potential applications in gas storage, catalysis, chemical sensing, molecular separations, etc. In this study, a homochiral pentyl cage compound was synthesized from a condensation reaction of (S,S)-1,2-pentyl-1,2-diaminoethane and 1,3,5-triformylbenzene. The imine-linked pentyl cage diluted with a polysiloxane (OV-1701) was explored as a novel stationary phase for high-resolution gas chromatographic separation of organic compounds. Some positional isomers were baseline separated on the pentyl cage-coated capillary column. In particular, various types of enantiomers including chiral alcohols, esters, ethers and epoxides can be resolved without derivatization on the pentyl cage-coated capillary column. The reproducibility of the pentyl cage-coated capillary column for separation was investigated using nitrochlorobenzene and styrene oxide as analytes. The results indicate that the column has good stability and separation reproducibility after being repeatedly used. This work demonstrates that molecular organic cage compounds could become a novel class of chiral separation media in the near future.Keywords:porous organic cage;capillary column;chiral stationary phase;chiral separation;gas chromatography
研究领域:
分析化学
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材料科学
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DOI
PubMed
高影响因子
Nanoscale Advances
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2023
·Vol. 5
·期 23
·6606-6616
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IF 4.7
Taotao Feng,Jiaxu Liu,Xiaoyan Zhang,Daidi Fan,Yunpeng Bai
In the past decade, virus-like particles (VLPs) that can encapsulate single or multiple enzymes have been studied extensively as typical nanoreactors for biocatalysis in vitro, yet their catalytic efficiencies are usually inadequate for real applications. These biocatalytic nanoreactors should be engineered like their free-enzyme counterparts to improve their catalytic performance for potential applications. Herein we engineer biocatalytic VLPs for the enhanced synthesis of chiral alcohols. Different methods including directed evolution were applied to the entire bacteriophage P22 VLPs (except the coat protein), which encapsulated a carbonyl reductase from Scheffersomyces stipitis (SsCR) and a glucose dehydrogenase from Bacillus megaterium (BmGDH) in their capsids. The best variant, namely M5, showed an enhanced turnover frequency (TOF, min−1) up to 15-fold toward the majority of tested aromatic prochiral ketones, and gave up to 99% enantiomeric excess in the synthesis of chiral alcohol pharmaceutical intermediates. A comparison with the mutations of the free-enzyme counterparts showed that the same amino acid mutations led to different changes in the catalytic efficiencies of free and confined enzymes. Finally, the engineered M5 nanoreactor showed improved efficiency in the scale-up synthesis of chiral alcohols. The conversions of three substrates catalyzed by M5 were all higher than those catalyzed by the wild-type nanoreactor, demonstrating that enzyme-encapsulating VLPs can evolve to enhance their catalytic performance for potential applications.
研究领域:
生物化学
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合成生物学
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酶学
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DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
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2016
·
IF 2.667
Ping Wei,Jia-Xin Gao,Gao-Wei Zheng,Hong Wu,Min-Hua Zong,Wen-Yong Lou
The novel anti-Prelog stereospecific carbonyl reductase from Acetobacter sp. CCTCC M209061 was successfully expressed in E. coli combined with glucose dehydrogenase (GDH) to construct an efficient whole-cell biocatalyst with coenzyme NADH regeneration. The enzymatic activity of GAcCR (AcCR with a GST tag) reached 304.9 U/g-dcw, even 9 folds higher than that of wild strain, and the activity of GDH for NADH regeneration recorded 46.0 U/mg-protein in the recombinant E. coli . As a whole-cell biocatalyst, the recombinant E. coli BL21(DE3)pLysS (pETDuet- gaccr - gdh ) possessed a broad substrate spectrum for kinds of carbonyl compounds with encouraging yield and stereoselectivity. Besides, the asymmetric reduction of ethyl 4-chloroacetoacetate (COBE) to optically pure ethyl 4-chloro-3-hydroxybutyrate (CHBE) catalyzed by the whole-cell biocatalyst was systematically investigated. Under the optimal reaction conditions, the optical purity of CHBE was over 99% e.e. for ( S )-enantiomer, and the initial rate and product yield reached 8.04 μmol/min and 99.4%, respectively. Moreover, the space-time yield was almost 20 folds higher than that catalyzed by the wild strain. Therefore, a new, high efficiency biocatalyst for asymmetric reductions was constructed successfully, and the enantioselective reduction of prochiral compounds using the biocatalyst was a promising approach for obtaining enantiopure chiral alcohols.
研究领域:
生物工程
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合成生物学
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DOI
PubMed
高影响因子
Bioresources and Bioprocessing
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2017
·Vol. 4
·期 1
·1-12
·
IF 0
Wei Ping,Cui Yu-Han,Zong Min-Hua,Xu Pei,Zhou Jian,Lou Wen-Yong
Background
Acetobacter sp. CCTCC M209061 could catalyze carbonyl compounds to chiral alcohols following anti-Prelog rule with excellent enantioselectivity. Therefore, the enzymatic characterization of carbonyl reductase (CR) from Acetobacter sp. CCTCC M209061 needs to be investigated. Results A CR from Acetobacter sp. CCTCC M209061 (AcCR) was cloned and expressed in E. coli . AcCR was purified and characterized, finding that AcCR as a dual coenzyme-dependent short-chain dehydrogenase/reductase (SDR) was more preferred to NADH for biocatalytic reactions. The AcCR was activated and stable when the temperature was under 35 °C and the pH range was from 6.0 to 8.0 for the reduction of 4′-chloroacetophenone with NADH as coenzyme, and the optimal temperature and pH were 45 °C and 8.5, respectively, for the oxidation reaction of isopropanol with NAD + . The enzyme showed moderate thermostability with half-lives of 25.75 h at 35 °C and 13.93 h at 45 °C, respectively. Moreover, the AcCR has broad substrate specificity to a range of ketones and ketoesters, and could catalyze to produce chiral alcohol with e.e. >99% for the majority of tested substrates following the anti-Prelog rule. Conclusions The recombinant AcCR exhibited excellent enantioselectivity, broad substrate spectrum, and highly stereoselective anti-Prelog reduction of prochiral ketones. These results suggest that AcCR is a powerful catalyst for the production of anti-Prelog alcohols. The biocatalytic reactions conducted with the recombinant AcCR
研究领域:
生物化学
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酶工程
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工业微生物学
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DOI
PubMed
LETTERS IN APPLIED MICROBIOLOGY
·
2021
·Vol. 72
·期 4
·399-407
·
IF 2.858
Wang N.,Xu Y.,Peng C.,Wang X.,Wei Y.,Li K.,Wang S.,Xu A.,Gao J.
A strain NQ1, which showed efficient asymmetric reduction of 3,5‐bis(trifluoromethyl) acetophenone (BTAP) to enantiopure (S)‐[3,5‐bis(trifluoromethyl)phenyl]ethanol ((S)‐BTPE), which is the key intermediate for the synthesis of a receptor antagonist and antidepressant, was isolated from a soil sample. Based on its morphological and internal transcribed spacer sequence, the strain NQ1 was identified to be Rhodotorula mucilaginosa NQ1. Some key reaction parameters involved in the bioreduction catalyzed by whole cells of R. mucilaginosa NQ1 were subsequently optimized, and the optimized conditions for the synthesis of (S)‐BTPE were determined to be as follows: 5·0 ml phosphate buffer (200 mmol l−1, pH 7·0), 80 mmol l−1 of BTAP, 250 g (wet weight) l−1 of resting cell, 35 g l−1 of glucose and a reaction for 18 h at 30°C and 180 rev min−1. The strain NQ1 exhibited a best yield of 99% and an excellent enantiomeric excess of 99% for the preparation of (S)‐BTPE under the above optimal conditions, and could also asymmetrically reduce a variety of bulky prochiral carbonyl compounds to their corresponding optical hydroxyl compound with excellent enantioselectivity. These results indicated that R. mucilaginosa NQ1 had a good capacity to reduce BTAP to its corresponding (S)‐BTPE, and might be a new potential biocatalyst for the production of valuable chiral hydroxyl compounds in industry.
研究领域:
微生物学
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生物催化
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有机化学
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DOI
高影响因子
Molecular Catalysis
·
2019
·
IF 2.938
Ping Wei,Ze-Wang Guo,Xiao-Ling Wu,Shan Liang,Xiao-Yang Ou,Pei Xu,Min-Hua Zong,Ji-Guo Yang,Wen-Yong Lou
Chiral alcohols and their derivatives are vital building blocks to synthesize pharmaceutical drugs and high-valued chemicals. Wild-type carbonyl reductase Ac CR from Acetobacter sp. has ideal enantioselectivity toward 11 prochiral substrates ( e.e. >99%) but poor activity. In this work, a semi-rational engineering was performed to enhance the activity of Ac CR. Fortunately, three positive double-mutants (mut-E144A/G152 L, mut-G152 L/Y189 N, and mut-I147 V/G152 L) with specific activity 17–61 folds higher than that of enzyme without modified were achieved. Kinetic studies suggested that the catalytic efficiencies ( k cat / K m ) of these mutants were also well enhanced. Finally, these modified mut- Ac CRs were successfully applied in asymmetric reductions of 11 structurally diverse prochiral substrates (200 mM) with excellent product yields (76.8%–99.1%) and enantiomeric excess ( e.e. >99%), which provides an alternative strategy for efficient synthesis of chiral alcohols for pharmaceuticals industry with ideal yield and enantioselectivity.
研究领域:
生物化学
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酶工程
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制药工业
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产品关联
DOI
高影响因子
Catalysis Science & Technology
·
2019
·Vol. 10
·期 1
·70-78
·
IF 5.726
Zeyu Yang,Hengwei Fu,Wenjie Ye,Youyu Xie,Qinghai Liu,Hualei Wang,Dongzhi Wei
Alcohol dehydrogenases (ADHs) together with the economical substrate-coupled cofactor regeneration system play a pivotal role in the asymmetric synthesis of chiral alcohols; however, severe challenges concerning the poor tolerance of enzymes to 2-propanol and the adverse effects of the by-product, acetone, limit its applications, causing this strategy to lapse. Herein, a novel ADH gene smadh2 was identified from Stenotrophomonas maltophilia by traditional genome mining technology. The gene was cloned into Escherichia coli cells and then expressed to yield SmADH2. SmADH2 has a broad substrate spectrum and exhibits excellent tolerance and superb activity to 2-propanol even at 10.5 M (80%, v/v) concentration. Moreover, a new thermostatic bubble column reactor (TBCR) system is successfully designed to alleviate the inhibition of the by-product acetone by gas flow and continuously supplement 2-propanol. The organic waste can be simultaneously recovered for the purpose of green synthesis. In the sustainable system, structurally diverse chiral alcohols are synthesised at a high substrate loading (>150 g L−1) without adding external coenzymes. Among these, about 780 g L−1 (6 M) ethyl acetoacetate is completely converted into ethyl (R)-3-hydroxybutyrate in only 2.5 h with 99.9% ee and 7488 g L−1 d−1 space–time yield. Molecular dynamics simulation results shed light on the high catalytic activity toward the substrate. Therefore, the high 2-propanol tolerance SmADH2 with the TBCR system proves to be a potent biocatalytic strategy for the synthesis of chiral alcohols on an industrial scale.
研究领域:
生物化学
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工业生物技术
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环境科学
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产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2018
·
IF 5.123
Zhenyu Lu,Xiaotian Lu,Yanhui Zhong,Yufei Hu,Gongke Li,Runkun Zhang
Isomers discrimination plays a vital role in modern chemistry , and development of efficient and rapid method to achieve this aim has attracted a great deal of interest. In this work, a novel carbon dot-decorated chiral porous organic cage hybrid nanocomposite (CD@RCC3) was prepared and used to fabricate fluorescent sensor. The resultant CD@RCC3 was characterized by using a range of techniques, finding that CD@RCC3 possesses strong and stable fluorescent property in common organic solvents , especially it exhibits chiral property. The potential application of CD@RCC3 in fluorescence sensing was demonstrated by isomers discrimination. The designed sensor was successfully used to rapid discriminate nitrophenol isomers. Meanwhile, it exhibited differentiation ability towards phenylalaninol and phenylethanol enantiomers . Our work enriches the type of synthetic materials for fluorescence sensing , and provides a simple method for distinguishing structural isomers and chiral isomers.
研究领域:
化学
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材料科学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）