Amine transaminases in chiral amines synthesis: recent advances and challenges
Transaminases, which catalyze the stereoselective transfer of an amino group between an amino donor and a prochiral ketone substrate, are interesting biocatalytic tools for the generation of optically pure chiral amines. In particular, amine transaminases (ATAs) are of industrial interest because th...
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| Published in | World journal of microbiology & biotechnology Vol. 34; no. 1; pp. 13 - 10 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
Dordrecht
Springer Netherlands
01.01.2018
Springer Nature B.V |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Transaminases, which catalyze the stereoselective transfer of an amino group between an amino donor and a prochiral ketone substrate, are interesting biocatalytic tools for the generation of optically pure chiral amines. In particular, amine transaminases (ATAs) are of industrial interest because they are capable of performing reductive amination reactions using a broad range of amine donors and acceptors. The most remarkable example of ATAs industrial application is in the production process of the anti-hyperglycaemic drug sitagliptin (Januvia
®
/Janumet
®
), which generated around 6 billion U.S. dollars of revenue to Merck in 2016. In this review, an update about the availability of microbial ATAs, discovered by both screening and database-mining approaches, or obtained by protein engineering of wild-type enzymes, will be provided. Current challenges in ATAs application and possible solutions will be also discussed. In particular, innovative biocatalytic process strategies aimed at the improvement of ATAs performances in chiral amines synthesis, e.g., using in situ product removal process strategies or flow reactors, will be presented. The progress in the industrial exploitation of these enzymes will be highlighted by selected examples of large-scale ATA-catalyzed processes. |
|---|---|
| AbstractList | Transaminases, which catalyze the stereoselective transfer of an amino group between an amino donor and a prochiral ketone substrate, are interesting biocatalytic tools for the generation of optically pure chiral amines. In particular, amine transaminases (ATAs) are of industrial interest because they are capable of performing reductive amination reactions using a broad range of amine donors and acceptors. The most remarkable example of ATAs industrial application is in the production process of the anti-hyperglycaemic drug sitagliptin (Januvia
/Janumet
), which generated around 6 billion U.S. dollars of revenue to Merck in 2016. In this review, an update about the availability of microbial ATAs, discovered by both screening and database-mining approaches, or obtained by protein engineering of wild-type enzymes, will be provided. Current challenges in ATAs application and possible solutions will be also discussed. In particular, innovative biocatalytic process strategies aimed at the improvement of ATAs performances in chiral amines synthesis, e.g., using in situ product removal process strategies or flow reactors, will be presented. The progress in the industrial exploitation of these enzymes will be highlighted by selected examples of large-scale ATA-catalyzed processes. Transaminases, which catalyze the stereoselective transfer of an amino group between an amino donor and a prochiral ketone substrate, are interesting biocatalytic tools for the generation of optically pure chiral amines. In particular, amine transaminases (ATAs) are of industrial interest because they are capable of performing reductive amination reactions using a broad range of amine donors and acceptors. The most remarkable example of ATAs industrial application is in the production process of the anti-hyperglycaemic drug sitagliptin (Januvia ® /Janumet ® ), which generated around 6 billion U.S. dollars of revenue to Merck in 2016. In this review, an update about the availability of microbial ATAs, discovered by both screening and database-mining approaches, or obtained by protein engineering of wild-type enzymes, will be provided. Current challenges in ATAs application and possible solutions will be also discussed. In particular, innovative biocatalytic process strategies aimed at the improvement of ATAs performances in chiral amines synthesis, e.g., using in situ product removal process strategies or flow reactors, will be presented. The progress in the industrial exploitation of these enzymes will be highlighted by selected examples of large-scale ATA-catalyzed processes. Transaminases, which catalyze the stereoselective transfer of an amino group between an amino donor and a prochiral ketone substrate, are interesting biocatalytic tools for the generation of optically pure chiral amines. In particular, amine transaminases (ATAs) are of industrial interest because they are capable of performing reductive amination reactions using a broad range of amine donors and acceptors. The most remarkable example of ATAs industrial application is in the production process of the anti-hyperglycaemic drug sitagliptin (Januvia®/Janumet®), which generated around 6 billion U.S. dollars of revenue to Merck in 2016. In this review, an update about the availability of microbial ATAs, discovered by both screening and database-mining approaches, or obtained by protein engineering of wild-type enzymes, will be provided. Current challenges in ATAs application and possible solutions will be also discussed. In particular, innovative biocatalytic process strategies aimed at the improvement of ATAs performances in chiral amines synthesis, e.g., using in situ product removal process strategies or flow reactors, will be presented. The progress in the industrial exploitation of these enzymes will be highlighted by selected examples of large-scale ATA-catalyzed processes. Transaminases, which catalyze the stereoselective transfer of an amino group between an amino donor and a prochiral ketone substrate, are interesting biocatalytic tools for the generation of optically pure chiral amines. In particular, amine transaminases (ATAs) are of industrial interest because they are capable of performing reductive amination reactions using a broad range of amine donors and acceptors. The most remarkable example of ATAs industrial application is in the production process of the anti-hyperglycaemic drug sitagliptin (Januvia®/Janumet®), which generated around 6 billion U.S. dollars of revenue to Merck in 2016. In this review, an update about the availability of microbial ATAs, discovered by both screening and database-mining approaches, or obtained by protein engineering of wild-type enzymes, will be provided. Current challenges in ATAs application and possible solutions will be also discussed. In particular, innovative biocatalytic process strategies aimed at the improvement of ATAs performances in chiral amines synthesis, e.g., using in situ product removal process strategies or flow reactors, will be presented. The progress in the industrial exploitation of these enzymes will be highlighted by selected examples of large-scale ATA-catalyzed processes. |
| ArticleNumber | 13 |
| Author | Monti, Daniela Ferrandi, Erica E. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29255954$$D View this record in MEDLINE/PubMed |
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| Keywords | Process development Protein engineering Amine transaminases Biocatalysis Chiral amines |
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| Publisher | Springer Netherlands Springer Nature B.V |
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| SubjectTerms | Amination Amines Applied Microbiology Biochemistry Biomedical and Life Sciences Biotechnology Chemical synthesis Environmental Engineering/Biotechnology Enzymes Life Sciences Microbiology Microorganisms Protein engineering Review Substrates Transaminases |
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| Title | Amine transaminases in chiral amines synthesis: recent advances and challenges |
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