Ammonia lyases and aminomutases as biocatalysts for the synthesis of α-amino and β-amino acids
TL;DR: The aim of this review is to review recent progress in the application of ammonia lyase and aminomutase enzymes to prepare enantiomerically pure α-amino and β-aminos acids.
About: This article is published in Current Opinion in Chemical Biology.The article was published on 2011-04-01. It has received 140 citations till now. The article focuses on the topics: Phenylalanine ammonia-lyase & Ammonia-Lyases.
Citations
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TL;DR: The advantages and applications of the most recent and attractive biocatalysts--reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases--will be discussed herein and exemplified by the syntheses of interesting compounds.
Abstract: The use of enzymes as catalysts for the preparation of novel compounds has received steadily increasing attention over the past few years. High demands are placed on the identification of new biocatalysts for organic synthesis. The catalysis of more ambitious reactions reflects the high expectations of this field of research. Enzymes play an increasingly important role as biocatalysts in the synthesis of key intermediates for the pharmaceutical and chemical industry, and new enzymatic technologies and processes have been established. Enzymes are an important part of the spectrum of catalysts available for synthetic chemistry. The advantages and applications of the most recent and attractive biocatalysts--reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases--will be discussed herein and exemplified by the syntheses of interesting compounds.
274 citations
TL;DR: Engineered variants of cytochrome P450_(BM3) have now been found to catalyze intramolecular C-H aminations in azide substrates, with mutations to two highly conserved residues significantly increased this activity.
Abstract: Nitrogen activation: Though P450 enzymes are masters of oxygen activation and insertion into C-H bonds, their ability to use nitrogen for the same purpose has so far not been explored. Engineered variants of cytochrome P450_(BM3) have now been found to catalyze intramolecular C-H aminations in azide substrates. Mutations to two highly conserved residues significantly increased this activity.
220 citations
TL;DR: This review provides an overview of the reported methods for enzymatic asymmetric synthesis of chiral amino acids, including asymmetric reductive amination of keto acids, asymmetric transfer of an amino group to keto fatty acids, enantioselective addition of ammonia to α,β-unsaturated acids, and aldol condensation ofan amino acid to aldehydes.
Abstract: Chiral amino acids are extensively applied in the pharmaceutical, food, cosmetic, agricultural, and feedstuff industries. The development of synthetic methodologies for optically pure amino acids has been driven by their significant applications. Among the various synthesis methods for the production of chiral amino acids, enzymatic asymmetric synthesis is a unique preparation strategy that shows great potential. This review provides an overview of the reported methods for enzymatic asymmetric synthesis of chiral amino acids, including asymmetric reductive amination of keto acids, asymmetric transfer of an amino group to keto acids, enantioselective addition of ammonia to α,β-unsaturated acids, and aldol condensation of an amino acid to aldehydes.
217 citations
TL;DR: This review provides a comprehensive overview of biocatalytic imine reduction and reductive amination of ketones, highlighting the natural roles, substrate scopes, structural features, and potential application fields of the involved enzymes.
Abstract: Chiral amines represent a prominent functional group in pharmaceuticals and agrochemicals and are hence attractive targets for asymmetric synthesis. Since the pharmaceutical industry has identified biocatalysis as a valuable tool for synthesising chiral molecules with high enantiomeric excess and under mild reaction conditions, enzymatic methods for chiral amine synthesis are increasing in importance. Among the strategies available in this context, the asymmetric reduction of imines by NAD(P)H-dependent enzymes and the related reductive amination of ketones have long remained underrepresented. However, recent years have witnessed an impressive progress in the application of natural or engineered imine-reducing enzymes, such as imine reductases, opine dehydrogenases, amine dehydrogenases, and artificial metalloenzymes. This review provides a comprehensive overview of biocatalytic imine reduction and reductive amination of ketones, highlighting the natural roles, substrate scopes, structural features, and potential application fields of the involved enzymes.
175 citations
TL;DR: This review surveys the known bioactive β-amino acid-containing natural products including nonribosomal peptides, macrolactam polyketides, and nucleoside-β-AMino acid hybrids and the mechanisms of β-Amino acid incorporation into natural products.
172 citations
References
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TL;DR: The hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features ofpromiscuous enzyme functions are addressed.
Abstract: Many, if not most, enzymes can promiscuously catalyze reactions, or act on substrates, other than those for which they evolved. Here, we discuss the structural, mechanistic, and evolutionary implications of this manifestation of infidelity of molecular recognition. We define promiscuity and related phenomena and also address their generality and physiological implications. We discuss the mechanistic enzymology of promiscuity—how enzymes, which generally exert exquisite specificity, catalyze other, and sometimes barely related, reactions. Finally, we address the hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features of promiscuous enzyme functions.
1,153 citations
Additional excerpts
...Such a duality of mechanisms could be viewed as an example of enzyme promiscuity in which two alternative approaches are used to catalyse ostensibly the same type of process [15,16]....
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TL;DR: Significant developments have occurred recently in enzyme function and properties, particularly with respect to library design, screening methodology, applications in synthetic transformations and strategies for the generation of new enzyme function.
Abstract: Enzymes are increasingly being used as biocatalysts in the generation of products that have until now been derived using traditional chemical processes. Such products range from pharmaceutical and agrochemical building blocks to fine and bulk chemicals and, more recently, components of biofuels. For a biocatalyst to be effective in an industrial process, it must be subjected to improvement and optimization, and in this respect the directed evolution of enzymes has emerged as a powerful enabling technology. Directed evolution involves repeated rounds of (i) random gene library generation, (ii) expression of genes in a suitable host and (iii) screening of libraries of variant enzymes for the property of interest. Both in vitro screening–based methods and in vivo selection–based methods have been applied to the evolution of enzyme function and properties. Significant developments have occurred recently, particularly with respect to library design, screening methodology, applications in synthetic transformations and strategies for the generation of new enzyme function.
693 citations
"Ammonia lyases and aminomutases as ..." refers background in this paper
...Current Opinion in Chemical Biology 2011, 15:234–240 techniques such as directed evolution [38,39] and rational protein engineering to be applied to provide biocatalysts with broader application....
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TL;DR: Combined with protein engineering, the catalytic promiscuity of enzymes may broadly extend their usefulness in organic synthesis.
Abstract: Biocatalysis has expanded rapidly in the last decades with the discoveries of highly stereoselective enzymes with broad substrate specificity. A new frontier for biocatalysis is broad reaction specificity, where enzymes catalyze alternate reactions. Although often under-appreciated, catalytic promiscuity has a natural role in evolution and occasionally in the biosynthesis of secondary metabolites. Examples of catalytic promiscuity with current or potential applications in synthesis are reviewed here. Combined with protein engineering, the catalytic promiscuity of enzymes may broadly extend their usefulness in organic synthesis.
528 citations
Additional excerpts
...Such a duality of mechanisms could be viewed as an example of enzyme promiscuity in which two alternative approaches are used to catalyse ostensibly the same type of process [15,16]....
[...]
TL;DR: Emphasis is placed on the development of methods to make laboratory evolution faster and more efficient, thus providing chemists and biotechnologists with a rich and non-ending source of robust and selective catalysts for a variety of useful applications.
Abstract: Asymmetric catalysis plays a key role in modern synthetic organic chemistry, with synthetic catalysts and enzymes being the two available options. During the latter part of the last century the use of enzymes in organic chemistry and biotechnology experienced a period of rapid growth. However, these biocatalysts have traditionally suffered from several limitations, including in many cases limited substrate scope, poor enantioselectivity, insufficient stability, and sometimes product inhibition. During the last 15 years, the genetic technique of directed evolution has been developed to such an extent that all of these long-standing problems can be addressed and solved. It is based on repeated cycles of gene mutagenesis, expression, and screening (or selection). This Review focuses on the directed evolution of enantioselective enzymes, which constitutes a fundamentally new approach to asymmetric catalysis. Emphasis is placed on the development of methods to make laboratory evolution faster and more efficient, thus providing chemists and biotechnologists with a rich and non-ending source of robust and selective catalysts for a variety of useful applications.
468 citations
"Ammonia lyases and aminomutases as ..." refers background in this paper
...Current Opinion in Chemical Biology 2011, 15:234–240 techniques such as directed evolution [38,39] and rational protein engineering to be applied to provide biocatalysts with broader application....
[...]
17 Feb 2010
TL;DR: In this article, the authors presented a method for the preparation of Imines by using catalytic asymmetric Nucleophilic Addition to Achiral Iminus.
Abstract: Preface STEREOSELECTIVE SYNTHESIS OF ALPHA-BRANCHED AMINES BY NUCLEOPHILIC ADDITION OF UNSTABILIZED CARBANIONS TO IMINES Introduction Overview of the Methods for the Preparation of Imines Chiral Auxiliary-Based Approaches Catalytic Asymmetric Nucleophilic Addition to Achiral Imines Conclusion ASYMMETRIC METHODS FOR RADICAL ADDITION TO IMINO COMPOUNDS Background and Introduction Intermolecular Radical Addition Chiral N-Acylhydrazones Asymmetric Catalysis of Radical Addition Closing Remarks ENANTIOSELECTIVE SYNTHESIS OF AMINES BY CHIRAL BRONSTED ACID CATALYSTS Introduction Carbon-Carbon Bond Forming Reactions Carbon-Hydrogen Bond Forming Reactions Carbon-Heteroatom Bond Forming Reactions Conclusion REDUCTION OF IMINES WITH TRICHLOROSILANE CATALYZED BY CHIRAL LEWIS BASES Introduction Formamides as Lewis-Basic Organocatalysts in Hydrosilylation of Imines Other Amides as Organocatalysts in Hydrosilylation of Imines Sulfinamides as Organocatalysts in Hydrosilylation of Imines Supported Organocatalysts in Hydrosilylation of Imines Mechanistic Considerations Synthetic Applications Conclusions Typical Procedures for the Catalytic Hydrosilylation of Imines CATALYTIC, ENANTIOSELECTIVE VINYLOGOUS MANNICH REACTIONS Introduction Vinylogous Mukaiyama-Mannich Reactions of Silyl Dienolates Direct Vinylogous Mannich Reactions of Unmodified Substrates Miscellaneous Conclusion CHIRAL AMINES FROM TRANSITION-METAL-MEDIATED HYDROGENATION AND TRANSFER HYDROGENATION Scope and Related Publications Chiral Amines with a Disubstituted Nitrogen Atom, HNRR1 Chiral Amines with Trisubstituted Nitrogen, NRR1R2 Conclusion ASYMMETRIC REDUCTIVE AMINATION Introduction Transition Metal-Mediated Homogenous Reductive Amination Enantioselective Organocatalytic Reductive Amination Diastereoselective Reductive Amination Conclusions ENANTIOSELECTIVE HYDROGENATION OF ENAMINES WITH MONODENTATE PHOSPHORUS LIGANDS Introduction Asymmetric Hydrogenation of Enamides Asymmetric Hydrogenation of N,N-Dialkyl Enamines Conclusion and Outlook BIDENTATE LIGANDS FOR ENANTIOSELECTIVE ENAMIDE REDUCTION Introduction Catalytic Enantioselective Hydrogenation of Enamides Conclusions ENANTIOSELECTIVE REDUCTION OF NITROGEN-BASED HETEROAROMATIC COMPOUNDS Asymmetric Hydrogenation of Quinolines Asymmetric Hydrogenation of Isoquinolines Asymmetric Hydrogenation of Pyrroles Asymmetric Hydrogenation of Quinoxalines Asymmetric Hydrogenation of Pyridine Derivatives Summary and Outlook ASYMMETRIC HYDROAMINATION Introduction: Synthesis of Amines via Hydroamination Hydroamination of Simple, Nonactivated Alkenes Hydroamination of Dienes, Allenes, and Alkynes Hydroamination with Enantiomerical Pure Amines Synthesis of Chiral Amines via Tandem Hydroamination/Hydrosilylation Conclusions Experimental Section ENANTIOSELECTIVE C-H AMINATION Introduction Background Racemic C-H Amination Substrate-Controlled Chiral Amine Synthesis via C-H Amination Enantioselective C-H Amination of Achiral Substrates Conclusion CHIRAL AMINES DERIVED FROM ASYMMETRIC AZA-MORITA-BAYLIS-HILLMAN REACTION Introduction Recent Mechanistic Insights Asymmetric Aza-MBH Reaction Chiral Auxiliary-Induced Diastereoselective Aza-MBH Reaction Chiral Teriary Amine Catalysts Chiral Phosphine Catalysts Chiral Bifunctional N-Heterocyclic Carbenes Chiral Ionic Liquids as Reaction Medium Aza-MBH-Type Reaction to Obtain Chiral Amines Strategies for the Removal of Protecting Groups Selected Typical Experimental Procedures Summary and Outlook BIOCATALYTIC ROUTES TO NONRACEMIC CHIRAL AMINES Introduction Kinetic Resolution of Racemic Amines DKR and Deracemization of Amines Asymmetric Synthesis of Amines Using Transaminases Conclusions and Future Perspectives
464 citations