Chiral Various synthetic strategies employing these enzymes

Chiral amines are the valuable constituents of many important pharmaceutical compounds or their intermediates. It is estimated that nearly 40-45% pharmaceutical drugs contain chiral amine scaffolds in their structures. The major challenges faced by the chemical synthesis of enantiopure amines are use of toxic chemicals, formation of large number of by-products, multi-step synthesis methods, thereby increasing the cost of the method. To this end, cost-effective and sustainable biocataltic methods are maturing and proven to be the proficient alternatives for the synthesis of chiral amines in enantiometrically pure forms.  Enzymes such as lipases, transaminase, amine oxidase, amine dehydrogenase, ammonia lyases, imine reductase, engineered P450 monooxygenase, Pictet-Spenglerase and barberine bridge enzyme, etc can be useful for the biocatalytic synthesis of various chiral amines. Here we report the recent progress achieved and current perspectives in the enzymatic synthesis of chiral amines using potential enzymes such as transaminases, imine reductases, amine dehydrogenase and amine oxidase. Various synthetic strategies employing these enzymes are currently undergoing and can potentially be used for the industrial synthesis of chiral amines. Protein engineering approaches, playing critical role in improving the enzyme pool and the substrate scope thereof for the synthesis of many important pharmaceuticals and chemicals, are also emphasized. Enzymatic synthesis of chiral amines is increasingly expanding and will continue to be one of the most interesting topics in ‘greener’ synthetic approaches. The stunning advances in the understanding of the complex cellular cascades and their molecular details have shifted the use of enzymes as major foci in the field of catalysis. Biocatalysis has emerged as a competent and superior alternative to traditional organo-catalysis for the production of fine chemicals, pharmaceuticals and agricultural products. Enzyme-mediated are well recognized for asymmetric transformations because of their execution in mild conditions and shortened synthetic route.The use of biocatalysts does not require the activation of functional groups, thus the protection and deprotection steps generally required in the chemical synthesis are avoided. Also, the generation of fewer by-products while avoiding the use of toxic reagents, achievements of excellent chemo-, regio- and stereo-selectivities with high product yields give biocatalysts an upper hand over the chemical reactions.Last few decades have witnessed the surged demands of enantiopure pharmaceuticals owing to the regulations imposed by various regulatory agencies. Low efficacy of racemates, adverse effects caused by the opposite enantiomer are some of the major reasons which make synthesis of single enantiomer of distinct interest.  The increasing demands of enantiopure compounds in the pharmaceutical, fine chemicals and agricultural industries and the environmental restrictions approved by many economies requisite the effective integration of traditional chemical synthesis methods with that of enzymatic ‘greener’ approaches. As enzymes are obtained from renewable resources, they fulfill the basic demands of sustainable and green chemistry, proposed by Graedel et al. In this context, biocatalysis, an application of enzymes for the efficient and selective chemical transformations, has been recognized as a major ‘green technology’whichprovides sustainable synthetic methods towards a myriad number of chiral compounds. The increasing demands of enzyme-mediated synthesisof enantiopure compounds can be fulfilled by discovery of new biocatalysts.Screening of novel microorganisms and genome mining for the identification of new enzymes play pivotal role in enzyme-mediated synthesis. Therefore, the exploitation of these novel biocatalysts can prove as a massive addition to applications of biocatalysts for the industrial synthesis of various pharmaceuticals, fine chemicals and other important products.Also, the performance (Stabililty and reactivity) of already available biocatalysts can be further improved by various protein engineering tools.Chiral amines play important role as building blocks of many life-saving drugs and other industrially important chemicals such as agrochemicals. It has been estimated that nearly 40% of the currently used pharmaceuticals contain chiral amine functional groups in their structure. In this regard, ACS Green Chemistry Institute, Pharmaceutical Roundtable also has acknowledged the asymmetric synthesis of amines from prochiral ketones and ammonia as one of the top aspirational reactions challenging the pharmaceutical industry Enzymes such as ?-transaminase, amine oxidase, amine dehydrogenase, ammonia lyases, imine reductase, lipases, engineered P450 monooxygenase, Pictet-Spenglerase and barberine bridge enzyme can be useful for the biocatalytic synthesis of various chiral amines.Owing to their importance in various industries, an earlier progress in the field of enzymatic synthesis of chiral amines is elegantly reviewed in the past few years  This review endeavors to provide an account of four important enzymes, namely amine transaminases, imine reductases, amine dehydrogenases and amine oxidase. Advancements in their discovery, recent developments and the current perspectives in applications of these enzymes for the synthesis of chiral amines are discussed along with the landmark discoveries. The pivotal role played by protein engineering approaches in the improvement of these biocatalysts is also emphasized.  Transaminases (TAs) arguably are one of the largest groups of enzymes used in the synthesis of chiral amino acids and amine building blocks. As TAs play key roles in various cellular signaling and metabolic pathways, their presence is ubiquitous in nature. The history of transamination can be traced back to 1930, when Needham and coworkers observed the relationship between levels of amino acids such as L-glutamic acid, L-aspartic acid and oxaloacetic acid in the breast muscles of pigeon. Since the first demonstration of transamination in late 1930s, various transaminases have been discovered in the subsequent decades. Depending on their specificities towards various substrates, transaminases are generally classified as ?- or ?-TAs. Transaminases are classified based on the structures of the amino donor substrates, which are divided based on the presence and position of a negatively charged group with respect to the amino group being transferred. While ?-Transaminases (e.g. amino acid TAs) exclusively catalyze the amination of ?-keto acids, ?-TAs transfer an amino group attached to a primary carbon at least one carbon away from a carboxyl group. Also, compounds lacking any carboxyl groups, such as amines and ketones can serve as substrates for ?-TAs, thus making them potential biocatalysts for the synthesis of chiral amine compounds

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