The review compiles artificial cascades involving enzymes with a focus on the last 10 years. A cascade is defined as the combination of at least two reaction steps in a single reaction vessel without isolation of the intermediates, whereby at least one step is catalyzed by an enzyme. Additionally, cascades performed in vivo and in vitro are discussed separately, whereby in vivo cascades are defined here as cascades relying on cofactor recycling by the metabolism or on a metabolite from the living organism. The review introduces a systematic classification of the cascades according to the number of enzymes in the linear sequence and differentiates between cascades involving exclusively enzymes and combinations of enzymes with non-natural catalysts or chemical steps. Since the number of examples involving two enzymes is predominant, the two enzyme cascades are further subdivided according to the number, order, and type of redox steps. Furthermore, this classification differentiates between cascades where all reaction steps are performed simultaneously, sequentially, or in flow.
Multi-enzymatic cascade reactions, i.e., the combination of several enzymatic transformations in concurrent one-pot processes, offer considerable advantages: the demand of time, costs and chemicals for product recovery may be reduced, reversible reactions can be driven to completion and the concentration of harmful or unstable compounds can be kept to a minimum. This review summarizes the developments in multi-enzymatic cascades employed for the asymmetric synthesis of chiral alcohols, amines and amino acids, as well as for C À C bond formation. In addition, a general classification of biocatalytic cascade systems is provided and bioprocess engineering aspects associated with the topic are discussed.
Biocatalysis, using defined enzymes for organic transformations, has become a common tool in organic synthesis, which is also frequently applied in industry. The generally high activity and outstanding stereo-, regio-, and chemoselectivity observed in many biotransformations are the result of a precise control of the reaction in the active site of the biocatalyst. This control is achieved by exact positioning of the reagents relative to each other in a fine-tuned 3D environment, by specific activating interactions between reagents and the protein, and by subtle movements of the catalyst. Enzyme engineering enables one to adapt the catalyst to the desired reaction and process. A well-filled biocatalytic toolbox is ready to be used for various reactions. Providing nonnatural reagents and conditions and evolving biocatalysts enables one to play with the myriad of options for creating novel transformations and thereby opening new, short pathways to desired target molecules. Combining several biocatalysts in one pot to perform several reactions concurrently increases the efficiency of biocatalysis even further.
Chiral aminesr epresent ap rominentf unctional group in pharmaceuticals and agrochemicals and are hence attractive targets for asymmetric synthesis.S ince the pharmaceutical industry has identified biocatalysis as av aluablet oolf or synthesising chiral molecules with high enantiomeric excess and under mild reactionc onditions,e nzymatic methods for chiral amine synthesisa re increasing in importance.A mong the strategies available in this context, the asymmetric reductiono fi mines by NAD(P)Hdependent enzymes andt he related reductive amination of ketones have long remained underrepresented. However, recent years have witnessed an impressive progress in the applicationo fn atural or engineered imine-reducing enzymes,s uch as imine reductases,o pine dehydrogenases,a mine dehydrogenases, and artificial metalloenzymes.T his review provides ac omprehensive overview of biocatalytic imine reductiona nd reductive amination of ketones,h ighlightingt he natural roles,s ubstrate scopes,s tructural features, and potential applicationf ields of the involvedenzymes.1I ntroduction 2I mine Reduction in Nature 2. 1I ntroductionChiral amines represent the core structure of am yriad of natural products as well as man-made compounds of public demand, such as pharmaceuticals and agrochemicals (Figure 1). Accordingt o recent estimates,c hiral amine moieties are present in about 40% of active pharmaceutical ingredients (APIs) and 20% of agrochemicals.[1] Moreover, optically pure amines,a mino acids,a nd amino alcohols are frequently employed in chemical synthesis as chiral auxiliariesorr esolving agents.Theirp aramount importance across several chemical disciplines andi ndustrial sectors has made chiral amines anda mino acids attractive targets for asymmetrics ynthesis.E stablished approachesf or their preparation are the stereoselective addition of nucleophiles to imines (including the famous Mannich and Strecker reactions), asymmetric C À Ha mination and hydroamination, and the asymmetric reductiono fe namines and imines,w hich may either be pre-formed or may occur as intermediates in an asymmetric reductive amination process.[2] Metallo-or organocatalytic methodsf or asymmetric imine and enamine reductiona re broadly applied, and intense research efforts are devoted to the improvement of the scope and stereoselectivity of these processes. [2,3] In cases where established asymmetric synthesism ethodsa re inapplicable or fail to provide the desired optical purity, diastereomeric salt crystallisation is still widely used for the classical resolution of racemic amines or for upgrading the enantiomeric excess of an optically enriched product.[2d]Biocatalytic transformationsa re increasingly being recognised as an attractive optionf or the asymmetric synthesiso fc hiral molecules.[4] Particularly in the
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.