Article
Chemistry, Multidisciplinary
Fengwei Chang, Chengyi Wang, Qipeng Chen, Yongjin Zhang, Guohua Liu
Summary: The combination of biocatalysis and transition-metal catalysis can bridge synthetic gaps in chemical or biological processes, but the deactivation between enzymatic and chemical species poses a significant challenge. Researchers developed an encapsulated Au/carbene and free amine dehydrogenase co-catalyst system, enabling efficient hydration/amination enantioselective cascade reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Itziar Penafiel, Robert A. W. Dryfe, Nicholas J. Turner, Michael F. Greaney
Summary: The integration of electro and bio-catalysis offers new ways of making molecules under very mild, environmentally benign conditions. The combined process offers a new approach to amine alkylation with native alcohols, a key bond formation in the chemical economy that is currently achieved via precious metal-catalyzed hydrogen-borrowing technologies.
Article
Multidisciplinary Sciences
Shuke Wu, Chao Xiang, Yi Zhou, Mohammad Saiful Hasan Khan, Weidong Liu, Christian G. Feiler, Ren Wei, Gert Weber, Matthias Hohne, Uwe T. Bornscheuer
Summary: This study reports a simple, high-throughput, and low-equipment dependent growth selection system for improving the performance of three enzymes in the synthesis of chiral amines. The results show that this system can successfully enhance the specific activity of enzymes, providing a flexible tool for the engineering process.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Ewald P. J. Jongkind, Aurelie Fossey-Jouenne, Ombeline Mayol, Anne Zaparucha, Carine Vergne-Vaxelaire, Caroline E. Paul
Summary: Accessing chiral amines with high enantiomeric and diastereomeric excess was achieved through the development of a bi-enzymatic cascade using Old Yellow Enzyme family enzymes. Different unsaturated carbonyl substrates were successfully converted with up to 99% selectivity, showcasing the potential of this approach for diverse alkene substrates.
Article
Chemistry, Applied
Yuanyi Qian, Liliang Chu, Xiaoyan Zhang, Zhiwen Lu, Yunpeng Bai
Summary: Optically pure lactams have a wide range of applications, including the synthesis of agricultural bioactive compounds and pharmaceuticals. This study presents a two-step chemo-enzymatic strategy for the efficient stereoselective synthesis of chiral lactams using a natural amine dehydrogenase that has been engineered through directed evolution. The engineered enzyme showed improved activity and high stereoselectivity in the synthesis of gamma- and delta- lactams, indicating its potential as an efficient biocatalyst for the production of valuable chiral lactams.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Review
Biotechnology & Applied Microbiology
Andras Telek, Zsofia Molnar, Beata G. Vertessy, Gabor Tasnadi
Summary: This review summarizes the current knowledge of opines and opine-type chemicals, highlighting their diverse biochemical roles and potential as synthetic building blocks of bioactive compounds. The synthesis of opines involves the reductive amination of ketoacids with amino acids, which has high synthetic potential in producing enantiopure secondary amines. While only one enzyme has been used as a biocatalyst for this transformation, analysis suggests that more enzymes can be exploited in synthetic organic chemistry.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Chemistry, Physical
Eric J. Ma, Elina Siirola, Charles Moore, Arkadij Kummer, Markus Stoeckli, Michael Faller, Caroline Bouquet, Fabian Eggimann, Mathieu Ligibel, Dan Huynh, Geoffrey Cutler, Luca Siegrist, Richard A. Lewis, Anne-Christine Acker, Ernst Freund, Elke Koch, Markus Vogel, Holger Schlingensiepen, Edward J. Oakeley, Radka Snajdrova
Summary: This study evaluated machine-directed evolution as an enzyme engineering strategy and found that within one cycle, it yielded a library of high-activity mutants with a significantly different activity distribution compared to traditional directed evolution. Structure-guided analysis suggested that linear additivity might provide a simple explanation for the effectiveness of machine-directed evolution in accessing chiral molecules.
Article
Chemistry, Multidisciplinary
Weixi Kong, Yunting Liu, Chen Huang, Liya Zhou, Jing Gao, Nicholas J. Turner, Yanjun Jiang
Summary: We report the engineering of an amine dehydrogenase (AmDH) from Jeotgalicoccus aerolatus for the direct asymmetric reductive amination of heteroaryl ketones. The engineered enzyme exhibited excellent conversions and enantioselectivities, even for ketones with bulky alkyl chains. Directed evolution based on molecular docking was used to enhance the enzyme's activity by enlarging the active pocket with a more hydrophobic entrance. The engineered enzyme was also applied in the synthesis of pharmaceutically relevant amines and a key intermediate of chiral pincer ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Matus Gajdos, Jendrik Wagner, Felipe Ospina, Antonia Koehler, Martin K. M. Engqvist, Stephan C. Hammer
Summary: In this study, a fatty acid hydratase from Marinitoga hydrogenitolerans was identified and evolved for the highly enantioselective hydration of styrenes, resulting in chiral 1-arylethanols. The evolved enzyme exhibited remarkable asymmetric styrene hydration activity in the absence of small molecule activators. This engineered styrene hydratase enables the synthesis of chiral alcohols from simple alkenes and water with high enantioselectivity (>99 : 1 e.r.) and can be used on a preparative scale.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
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.
Review
Chemistry, Physical
Jianqiao Liu, Weixi Kong, Jing Bai, Yongxing Li, Lele Dong, Liya Zhou, Yunting Liu, Jing Gao, Ruth T. Bradshaw Allen, Nicholas J. Turner, Yanjun Jiang
Summary: This review discusses the importance and challenges of AmDHs in chiral-amine synthesis, as well as recent advances and engineering design strategies. By exploring the structures, mechanisms, and mutation studies of AmDHs, as well as the development of optimized reaction systems, guidance and direction are provided for improving the performance and efficiency of AmDHs.
Article
Chemistry, Physical
Zewang Guo, Denghui Chen, Qi Xiong, Miao Liang, Pengfei Li, Zehui Gong, Junzhi Qiu, Liaoyuan Zhang
Summary: In this study, a new LeuDH named PbLeuDH was heterologously over-expressed in Escherichia coli, followed by purification and characterization. PbLeuDH exhibited excellent catalytic efficiency for TMP and was used for high-yield L-Tle production through whole-cell biocatalysis. This research provides a competitive biocatalyst for green biosynthesis of L-Tle.
Article
Chemistry, Multidisciplinary
Christian M. Heckmann, Francesca Paradisi
Summary: The combination of biocatalysis and chemocatalysis can provide a powerful method for accessing chiral N-aryl amines in excellent enantioselectivity. The use of a bi-phasic buffer-toluene system and the ligand GPhos allows for a telescoped cascade with up to 89% overall conversion in the presence of excess alanine, without observed coupling to alanine.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Physical
Jeremy Steflik, Amelia Gilio, Michael Burns, Gideon Grogan, Rajesh Kumar, Russell Lewis, Carlos Martinez
Summary: This study reports a method for biocatalytic reductive amination reactions, which have high potential value in pharmaceutical synthesis. The researchers identified and engineered a RedAm enzyme to catalyze the synthesis of a key intermediate for a cyclin-dependent kinase (CDK) inhibitor. The optimized enzyme variant showed high productivity at high substrate concentrations (50-fold improvement over the wild-type). Crystal structures of both the wild-type and mutant enzymes were solved to elucidate the structural changes that improved the performance of the RedAm under process conditions. This work demonstrates the versatility and industrial utility of RedAm-catalyzed reductive amination by enabling the synthesis of a chiral intermediate on a multikilogram scale.
Article
Biochemistry & Molecular Biology
Chao Xiang, Shuke Wu, Uwe T. Bornscheuer
Summary: By performing directed evolution, a new enzyme variant VF-8M-E with significantly increased specific activity was obtained, which was successfully utilized to produce the key chiral amine intermediate in enantiopure form for Apremilast, representing a new enzymatic approach towards the synthesis of Apremilast.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
