☆ 4.8 Article

Simultaneous engineering of an enzyme's entrance tunnel and active site: the case of monoamine oxidase MAO-N

CHEMICAL SCIENCE (2017)

获取全文
添加到收藏夹

期刊

CHEMICAL SCIENCE
卷 8, 期 5, 页码 4093-4099

出版社

ROYAL SOC CHEMISTRY
DOI: 10.1039/c6sc05381e

关键词

-

类别

Chemistry, Multidisciplinary

资金

  1. Max-Planck-Society
  2. LOEWE Research Cluster SynBioChem
  3. Youth Innovation Promotion Association of the Chinese Academy of Sciences [2016166]

向作者/读者索取更多资源

Protocol

社区支持

Reagent

社区支持

A new directed evolution approach is presented to enhance the activity of an enzyme and to manipulate stereoselectivity by focusing iterative saturation mutagenesis (ISM) simultaneously on residues lining the entrance tunnel and the binding pocket. This combined mutagenesis strategy was applied successfully to the monoamine oxidase from Aspergillus niger (MAO-N) in the reaction of sterically demanding substrates which are of interest in the synthesis of chiral pharmaceuticals based on the benzo-piperidine scaffold. Reversal of enantioselectivity of Turner-type deracemization was achieved in the synthesis of (S)-1,2,3,4-tetrahydro-1-methyl-isoquinoline, (S)-1,2,3,4-tetrahydro-1-ethylisoquinoline and (S)-1,2,3,4-tetrahydro-1-isopropylisoquinoline. Extensive molecular dynamics simulations indicate that the altered catalytic profile is due to increased hydrophobicity of the entrance tunnel acting in concert with the altered shape of the binding pocket.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Chemistry, Applied

Asymmetric Synthesis of N-Substituted γ-Amino Esters and γ-Lactams Containing α,γ-Stereogenic Centers via a Stereoselective Enzymatic Cascade

Ming Li, Yunfeng Cui, Zefei Xu, Xi Chen, Jinhui Feng, Min Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: This study presents an enzymatic cascade reaction for the efficient synthesis of chiral intermediates with alpha,gamma-stereogenic centers, providing a new route for the synthesis of various bioactive compounds.

ADVANCED SYNTHESIS & CATALYSIS (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

Engineering a Carbonyl Reductase for Scalable Preparation of (S)-3-Cyclopentyl-3-hydroxypropanenitrile, the Key Building Block of Ruxolitinib

Yunfeng Cui, Liangyan Zhu, Xi Chen, Jinhui Feng, Qiaqing Wu, Dunming Zhu

Summary: The study demonstrated a method for synthesizing the key precursor for ruxolitinib using PhADH to bioreduce 3-cyclopentyl-3-ketopropanenitrile. Rational engineering of the PhADH enzyme led to the double mutant H93C/A139L, which showed improved enantioselectivity and specific activity. This mutant enzyme was found to be effective in reducing beta-substituted-beta-ketonitriles at high concentrations.

CHEMBIOCHEM (2022)

添加到收藏夹
Review Chemistry, Multidisciplinary

Biotransformation Enables Innovations Toward Green Synthesis of Steroidal Pharmaceuticals

Jinhui Feng, Qiaqing Wu, Dunming Zhu, Yanhe Ma

Summary: Steroids have been widely used in birth control, prevention, and treatment of various diseases, and they represent a major sector in the global pharmaceutical market. Advances in genetic and metabolic engineering have led to the production of steroidal precursors from phytosterols, replacing the use of sapogenins as starting materials. Synthetic biology holds promise in the design and construction of microbial cell factories for the industrial production of steroidal intermediates and APIs, leading to a greener steroidal pharmaceutical industry.

CHEMSUSCHEM (2022)

添加到收藏夹
Article Chemistry, Physical

Asymmetric Synthesis of Both Enantiomers of Dimethyl 2-Methylsuccinate by the Ene-Reductase-Catalyzed Reduction at High Substrate Concentration

Jiacheng Li, Jianjiong Li, Yunfeng Cui, Min Wang, Jinhui Feng, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: This study identified three ene-reductases with high substrate tolerance and stereoselectivity towards dimethyl citraconate, dimethyl mesaconate, and dimethyl itaconate, providing an efficient methodology for the enantiocomplementary production of optically pure dimethyl 2-methylsuccinate.

CATALYSTS (2022)

添加到收藏夹
Article Chemistry, Organic

Enantiodivergent Synthesis of 1-Heteroaryl Tetrahydroisoquinolines Catalyzed by Imine Reductases

Tingting Liu, Zefei Xu, Jinhui Feng, Shanshan Yu, Min Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: Two enantiocomplementary imine reductases (IREDs) with high enantioselectivity were identified through screening and engineering, which allowed the synthesis of a series of 1-heteroaryl tetrahydroisoquinolines with high to excellent ee values and isolated yields, providing an effective method for constructing pharmaceutically important alkaloids, including the intermediate of kinase inhibitor TAK-981.

ORGANIC LETTERS (2023)

添加到收藏夹
Article Chemistry, Physical

Desymmetric Reductive Amination of 1,3-Cyclopentadiones to Single Stereoisomer of fl-Amino Ketones with an All-Carbon Quaternary Stereocenter by Engineered Amine Dehydrogenases

Tong Lv, Jinhui Feng, Xi Chen, Yuyang Luo, Qiaqing Wu, Dunming Zhu, Yanhe Ma

Summary: Mutant amine dehydrogenases (LsAmDHs) were developed through directed evolution from L-phenylalanine dehydrogenase, enabling the asymmetric reductive amination of 2,2-disubstituted-1,3-cyclopentadiones with high yield. This study not only synthesized the corresponding stereoisomeric fi-amino ketones, but also provided a useful tool for addressing the challenges in asymmetric reductive amination of diketones.

ACS CATALYSIS (2023)

添加到收藏夹
Article Chemistry, Physical

Flipping the Substrate Creates a Highly Selective Halohydrin Dehalogenase for the Synthesis of Chiral 4-Aryl-2-oxazolidinones from Readily Available Epoxides

Chuanhua Zhou, Xi Chen, Tong Lv, Xu Han, Jinhui Feng, Weidong Liu, Qiaqing Wu, Dunming Zhu

Summary: In this study, a unique halohydrin dehalogenase (AbHheG) was found to have high activity and alpha/beta-regioselectivity toward the ring opening of racemic styrene oxide with cyanate but with poor stereoselectivity. By reshaping the substrate-binding site of AbHheG, a variant Y15M/N182S was obtained with excellent alpha/beta-regioselectivity and stereoselectivity. This work demonstrated that halohydrin dehalogenase is a useful biocatalyst for the synthesis of both enantiomers of 4-aryl-2-oxazolidinones from readily available racemic styrene oxides.

ACS CATALYSIS (2023)

添加到收藏夹
Article Chemistry, Organic

Semirational Engineering of a Thermostable Carbonyl Reductase for the Precision Synthesis of (2R,3R)-2-Methyl-2-benzyl-3-hydroxycyclopentanone and Its Analogues

Liangyan Zhu, Xi Chen, Jinhui Feng, Yunfeng Cui, Qiaqing Wu, Dunming Zhu

Summary: A mutant L91C/F93I of the thermostable carbonyl reductase CBCR from Cupriavidus sp. BIS7 was obtained through semirational engineering. The mutant L91C/F93I showed 4- to 36-fold enhanced activities toward 2-methyl-2-benzyl-1,3-cyclopentanedione and its analogues, affording the (2R,3R)-stereoisomers with >99% ee and >99% de. Enzyme-substrate docking studies revealed the molecular basis for the activity and stereoselectivity improvements.

JOURNAL OF ORGANIC CHEMISTRY (2023)

添加到收藏夹
Article Chemistry, Physical

Engineering a Carbonyl Reductase to Simultaneously Increase Activity Toward Bulky Ketone and Isopropanol for Dynamic Kinetic Asymmetric Reduction via Enzymatic Hydrogen Transfer

Hongliu Zhang, Xi Chen, Tong Lv, Qian Li, Weidong Liu, Jinhui Feng, Xiangtao Liu, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: In this study, a mutant M242F/Q245T of the carbonyl reductase from Sporobolomyces salmonicolor was found to enhance its activity toward both methyl 2-phthalimidomethyl-3-oxobutanoate(1a) and isopropanol, enabling the dynamic kinetic asymmetric reduction of 1a to a single stereoisomer of the product by hydrogen transfer from isopropanol. Structural and computational analysis suggested that the synergic effect of 242F and 245T reshaped the substrate entrance tunnel and enzyme active site. This study demonstrated that a carbonyl reductase can be engineered to improve its activity toward bulky ketones and isopropanol, and enable efficient preparation of the target chiral alcohol via substrate-coupled cofactor regeneration.

ACS CATALYSIS (2023)

添加到收藏夹
Article Chemistry, Multidisciplinary

Photoredox/Enzymatic Catalysis Enabling Redox-Neutral Decarboxylative Asymmetric C-C Coupling for Asymmetric Synthesis of Chiral 1,2-Amino Alcohols

Yiyin Liu, Liangyan Zhu, Xuemei Li, Yunfeng Cui, Atefeh Roosta, Jinhui Feng, Xi Chen, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: In this study, a redox-neutral photocatalysis/enzymatic catalysis system was developed for the asymmetric synthesis of chiral 1,2-amino alcohols via decarboxylative radical C-C coupling. This strategy not only enables the efficient synthesis of a series of chiral amino alcohols in a green and sustainable manner but also has potential for the synthesis of bioactive molecules through novel C-C radical coupling transformations.

JACS AU (2023)

添加到收藏夹
Article Chemistry, Organic

Enantiodivergent Synthesis of 1-Heteroaryl Tetrahydroisoquinolines Catalyzed by Imine Reductases

Tingting Liu, Zefei Xu, Jinhui Feng, Shanshan Yu, Min Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: Two highly enantioselective enantiocomplementary imine reductases (IREDs) were discovered through screening and enzyme engineering, which exhibited catalytic activity towards the reduction of 1-heteroaryl dihydroisoquinolines. By utilizing (R)-IR141-L172M/Y267F and (S)-IR40, a series of different 1-heteroaryl tetrahydroisoquinolines were efficiently synthesized with excellent enantioselectivity (82 to >99% ee) and high isolated yields (80 to 94%), providing an effective method for constructing pharmaceutically important alkaloids, including the intermediate of kinase inhibitor TAK-981.

ORGANIC LETTERS (2023)

添加到收藏夹
Article Chemistry, Multidisciplinary

Chemo-enzymatic synthesis of chiral 3-substituted tetrahydroquinolines by a sequential biocatalytic cascade and Buchwald-Hartwig cyclization

Zefei Xu, Jinhui Feng, Peiyuan Yao, Qiaqing Wu, Dunming Zhu

Summary: A general chemo-enzymatic approach for the efficient asymmetric synthesis of chiral 3-substituted tetrahydroquinolines has been developed, combining biocatalysis and the Buchwald-Hartwig cross-coupling reaction. The method involves a one-pot ene reductase (ERED)/imine reductase (IRED) cascade and successfully addresses the issue of racemization of the intermediate. This method offers a practical strategy for the construction of chiral 3-substituted tetrahydroquinolines.

GREEN CHEMISTRY (2023)

添加到收藏夹
Article Chemistry, Physical

Creating a new benzaldehyde lyase for atom-economic synthesis of chiral 1,2,4-butanetriol and 2-aminobutane-1,4-diol from formaldehyde

Yu Li, Peiyuan Yao, Shiqing Zhang, Jinhui Feng, Hao Su, Xiangtao Liu, Xiang Sheng, Qiaqing Wu, Dunming Zhu, Yanhe Ma

Summary: Selective activation and controllable transformation of formaldehyde is still a challenge, but researchers have engineered a benzaldehyde lyase to couple 3-hydroxypropanal and formaldehyde. They also identified a carbonyl reductase and a transaminase for the reduction or transamination of 1,4-dihydroxybutan-2-one. These enzymatic reactions were combined with chemocatalytic hydration of acrolein to synthesize optically pure 1,2,4-butanetriol and 2-aminobutane-1,4-diol. This study demonstrates a sustainable approach to the synthesis of high value-added chemicals from C1 molecules.

CHEM CATALYSIS (2023)

添加到收藏夹
Article Chemistry, Physical

Directed evolution of an alcohol dehydrogenase for the desymmetric reduction of 2,2-disubstituted cyclopenta-1,3-d ones by enzymatic hydrogen transfer

Hongliu Zhang, Liangyan Zhu, Jinhui Feng, Xiangtao Liu, Xi Chen, Qiaqing Wu, Dunming Zhu

Summary: In this study, the alcohol dehydrogenase TbADH from Thermoanaerobacter brockii was improved through structure-guided directed evolution, resulting in enhanced enzyme activity and efficient catalysis of specific substrates, leading to the synthesis of complex molecules with multiple chiral centres.

CATALYSIS SCIENCE & TECHNOLOGY (2022)

添加到收藏夹
Article Chemistry, Multidisciplinary

Iodide oxidation by ozone at the surface of aqueous microdroplets

Alexander M. Prophet, Kritanjan Polley, Gary J. Van Berkel, David T. Limmer, Kevin R. Wilson

Summary: The oxidation kinetics of iodide by ozone at the air-water interface is studied in single microdroplets. Molecular simulations and kinetic modeling are used to understand the underlying multiphase mechanism.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Aggregate assembly of ferrocene functionalized indium-oxo clusters

Rong Zhang, Jiajing Lan, Fei Wang, Shumei Chen, Jian Zhang

Summary: By utilizing 1,1'-ferrocene dicarboxylic acid as a chelating and surface protection ligand, we have synthesized multi-nuclear indium oxide clusters with varying nuclear sizes, including heptanuclear and thirteen-nuclear clusters. These clusters possess labile coordination sites, allowing for structural modification and self-assembly, resulting in the formation of various cluster structures.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Cucurbituril-based supramolecular host-guest complexes: single-crystal structures and dual-state fluorescence enhancement

Hui Wang, Hui Liu, Mingsen Wang, Jiaheng Hou, Yongjun Li, Yuancheng Wang, Yingjie Zhao

Summary: Two supramolecular complexes were prepared using CBs and M1, and their single-crystal structures were analyzed by SCXRD. The unexpected 1:2 self-assembly structure between M1 and CB[8] was discovered for the first time. These complexes exhibit unique photophysical properties and provide valuable information about the structure and photophysical properties of supramolecular complexes.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Engineering of cell-surface receptors for analysis of receptor internalization and detection of receptor-specific glycosylation

Chang-Hee Lee, Sookil Park, Sanggil Kim, Ji Young Hyun, Hyun Soo Lee, Injae Shin

Summary: The epidermal growth factor receptor (EGFR) is a cell-surface glycoprotein involved in cell proliferation and tumor development. This study used a fluorescently labeled EGFR to investigate its time-dependent endocytosis in live cells and found that appended glycans affect EGFR internalization. Additionally, the study detected sialic acid residues attached to EGFR on the live cell surface using FRET-based imaging. This research provides valuable insights into the cellular functions of EGFR.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Ultrasensitive detection of aromatic water pollutants through protein immobilization driven organic electrochemical transistors

Subhankar Sahu, Lokesh Kumar, Sumita Das, Dipti Gupta, Ruchi Anand

Summary: This study proposes a strategy that combines organic electronics with biosensor scaffolds to create a compact device for monitoring environmental aromatic pollution. By coupling biosensing protein MopR with an organic electrochemical transistor (OECT), a sensor module capable of efficient detection of phenol was designed. Exclusive phenol detection with minimal loss of sensitivity could be achieved in complex pollutant mixtures and real environmental samples.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Review Chemistry, Multidisciplinary

NiH-catalyzed C-N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons

Changseok Lee, Hyung-Joon Kang, Sungwoo Hong

Summary: The formation of C-N bonds through hydroamination reactions catalyzed by nickel hydrides has been a topic of recent interest. This approach offers a way to efficiently transform a variety of alkene and alkyne substrates into compounds enriched with C-N bonds. The review provides a concise overview of the underlying reaction mechanisms and aims to stimulate further progress in NiH-catalytic techniques and catalyst design.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Selective FRET nano probe based on carbon dots and naphthalimide-isatin for the ratiometric detection of peroxynitrite in drug-induced liver injury

Yueci Wu, Lu-Lu Sun, Hai-Hao Han, Xiao-Peng He, Weiguo Cao, Tony D. James

Summary: Drug-induced liver injury (DILI) is a common cause of acute liver failure in the USA and Europe, but most cases can be recovered or prevented by discontinuing the offending drug. Recent research has found that peroxynitrite (ONOO-) can be used as a potential indicator for early diagnosis of DILI, and there is an urgent need to establish a method to detect and track peroxynitrite in DILI cases. In this study, a FRET-based nano fluorescent probe CD-N-I was developed, which showed high selectivity and sensitivity in detecting peroxynitrite. The probe successfully detected exogenous peroxynitrite in live cells and endogenous peroxynitrite in APAP-induced liver injury of HepG2 cells.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Direct conversion of carboxylic acids to free thiols via radical relay acridine photocatalysis enabled by N-O bond cleavage

Dmitry L. Lipilin, Mikhail O. Zubkov, Mikhail D. Kosobokov, Alexander D. Dilman

Summary: This article describes a direct photocatalytic method for the thiolation of unprotected acids, which was previously challenging. By using a thionocarbonate reagent with an N-O bond, the efficient conversion of carboxylic acids to thiols is achieved.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Towards routine organic structure determination using Raman microscopy

Jason Malenfant, Lucille Kuster, Yohann Gagne, Kouassi Signo, Maxime Denis, Sylvain Canesi, Mathieu Frenette

Summary: Raman microscopy can reveal compound-specific vibrational fingerprints without sample preparation. The combination of efficient theoretical calculations and a user-friendly software can accurately predict peak positions and provide match scores to assist with structure determination.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Metal selectivity and translocation mechanism characterization in proteoliposomes of the transmembrane NiCoT transporter NixA from Helicobacter pylori

Jayoh A. Hernandez, Paul S. Micus, Sean Alec Lois Sunga, Luca Mazzei, Stefano Ciurli, Gabriele Meloni

Summary: Essential trace metals play crucial roles in the survival and virulence of bacterial pathogens. Helicobacter pylori requires nickel for colonization and persistence in the stomach, and NixA is an essential nickel transporter in this process. This study characterizes the selectivity and electrogenic nature of NixA-mediated nickel transport.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

A high-spin alkylperoxo-iron(III) complex with cis-anionic ligands: implications for the superoxide reductase mechanism

Tarali Devi, Kuheli Dutta, Jennifer Deutscher, Stefan Mebs, Uwe Kuhlmann, Michael Haumann, Beatrice Cula, Holger Dau, Peter Hildebrandt, Kallol Ray

Summary: This study emphasizes the importance of subtle electronic changes and secondary interactions in the stability of biologically relevant metal-dioxygen intermediates. It also shows that the role of the chloride ligand in stabilizing the Fe-III-(OOBu)-Bu-t moiety can extend to other anions, including the thiolate ligand.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Effects of altered backbone composition on the folding kinetics and mechanism of an ultrafast-folding protein

Jacqueline R. Santhouse, Jeremy M. G. Leung, Lillian T. Chong, W. Seth Horne

Summary: By studying the folding kinetics and mechanism of the BdpA sequence, researchers found that altering the backbone connectivity can affect protein folding. This suggests that protein mimetic chains have a significant degree of plasticity in transitioning between unfolded and folded states.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Strain induced reactivity of cyclic iminoboranes: the (2+2) cycloaddition of a 1H-1,3,2-diazaborepine with ethene

Divanshu Gupta, Ralf Einholz, Holger F. Bettinger

Summary: This study presents the first direct spectroscopic evidence of a cyclic seven-membered iminoborane. Compared to linear amino-iminoboranes, this cyclic iminoborane exhibits weakened bond strength and lower Lewis acidity value. The study suggests that the reduced ring strain of cyclic iminoborane prevents nitrogen fixation but allows facile (2 + 2) cycloaddition reaction with C2H4.

CHEMICAL SCIENCE (2024)

添加到收藏夹
Article Chemistry, Multidisciplinary

Unveiling the topology of partially disordered micro-crystalline nitro-perylenediimide with X-aggregate stacking: an integrated approach

Renny Mathew, Aniruddha Mazumder, Praveen Kumar, Julie Matula, Sharmarke Mohamed, Petr Brazda, Mahesh Hariharan, Brijith Thomas

Summary: This study reveals the packing arrangement of partially disordered nitro-perylenediimide (NO2-PDI) using a synergistic approach that combines 3D ED, ssNMR, and DFT techniques. By overcoming these challenges, this methodology opens up new avenues for material characterization, driving exciting advancements in the field.

CHEMICAL SCIENCE (2024)

添加到收藏夹
研讨会 海报 问题 讨论圈 基金 期刊 论文 科研社交 资讯集成 审稿人 关于我们 常见问题 移动App 隐私条款 使用条款
© Peeref 2019-2024. All rights reserved.