Process Understanding of Transamination Reaction in Chiral Pharmaceutical Intermediate Production Catalyzed by an Engineered Amine Transaminase.
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| Title: | Process Understanding of Transamination Reaction in Chiral Pharmaceutical Intermediate Production Catalyzed by an Engineered Amine Transaminase. |
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| Authors: | Perçin, Zeynep1 (AUTHOR) zeynep.percin@tuhh.de, Kleinbeck, Florian2 (AUTHOR), Bubenheim, Paul1 (AUTHOR), Ruch, Thomas2 (AUTHOR), Liese, Andreas1 (AUTHOR) liese@tuhh.de |
| Source: | ChemCatChem. 2/17/2025, Vol. 17 Issue 4, p1-6. 6p. |
| Subjects: | Tubular reactors, Entresto, Biochemical substrates, Equilibrium reactions, Bioconversion, Biocatalysis |
| Abstract: | Chiral amines are key building blocks for the synthesis of many active pharmaceutical ingredients (APIs). Biocatalytic routes offer significant advantages to provide sustainable access to such motifs on commercial scale, with sacubitril valsartan sodium hydrate as a recent example. In this study a deeper mechanistic and kinetic understanding of the central biocatalytic step in the synthesis of sacubitril valsartan sodium hydrate, applying the evolved transaminase CDX‐043, was gained. The equilibrium of the transamination reaction was investigated in detail, and two kinetic models (ping‐pong two‐substrate kinetics and Michaelis–Menten double substrate kinetics) were established, considering substrate and product inhibition. The determined equilibrium constant indicates that the equilibrium lies strongly on the product side. The results of the kinetic studies demonstrate that the transaminase reaction is in conformity with the Michaelis–Menten double substrate kinetic model. Product inhibition was found to be more severe than substrate inhibition. The application of a plug flow reactor (PFR) was shown to be the preferred reactor setup to reduce the occurring inhibition. [ABSTRACT FROM AUTHOR] |
| Copyright of ChemCatChem is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
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| Header | DbId: egs DbLabel: Engineering Source An: 184868149 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Process Understanding of Transamination Reaction in Chiral Pharmaceutical Intermediate Production Catalyzed by an Engineered Amine Transaminase. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Perçin%2C+Zeynep%22">Perçin, Zeynep</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> zeynep.percin@tuhh.de</i><br /><searchLink fieldCode="AR" term="%22Kleinbeck%2C+Florian%22">Kleinbeck, Florian</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bubenheim%2C+Paul%22">Bubenheim, Paul</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ruch%2C+Thomas%22">Ruch, Thomas</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liese%2C+Andreas%22">Liese, Andreas</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> liese@tuhh.de</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22ChemCatChem%22">ChemCatChem</searchLink>. 2/17/2025, Vol. 17 Issue 4, p1-6. 6p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Tubular+reactors%22">Tubular reactors</searchLink><br /><searchLink fieldCode="DE" term="%22Entresto%22">Entresto</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemical+substrates%22">Biochemical substrates</searchLink><br /><searchLink fieldCode="DE" term="%22Equilibrium+reactions%22">Equilibrium reactions</searchLink><br /><searchLink fieldCode="DE" term="%22Bioconversion%22">Bioconversion</searchLink><br /><searchLink fieldCode="DE" term="%22Biocatalysis%22">Biocatalysis</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Chiral amines are key building blocks for the synthesis of many active pharmaceutical ingredients (APIs). Biocatalytic routes offer significant advantages to provide sustainable access to such motifs on commercial scale, with sacubitril valsartan sodium hydrate as a recent example. In this study a deeper mechanistic and kinetic understanding of the central biocatalytic step in the synthesis of sacubitril valsartan sodium hydrate, applying the evolved transaminase CDX‐043, was gained. The equilibrium of the transamination reaction was investigated in detail, and two kinetic models (ping‐pong two‐substrate kinetics and Michaelis–Menten double substrate kinetics) were established, considering substrate and product inhibition. The determined equilibrium constant indicates that the equilibrium lies strongly on the product side. The results of the kinetic studies demonstrate that the transaminase reaction is in conformity with the Michaelis–Menten double substrate kinetic model. Product inhibition was found to be more severe than substrate inhibition. The application of a plug flow reactor (PFR) was shown to be the preferred reactor setup to reduce the occurring inhibition. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of ChemCatChem is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1002/cctc.202401405 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 1 Subjects: – SubjectFull: Tubular reactors Type: general – SubjectFull: Entresto Type: general – SubjectFull: Biochemical substrates Type: general – SubjectFull: Equilibrium reactions Type: general – SubjectFull: Bioconversion Type: general – SubjectFull: Biocatalysis Type: general Titles: – TitleFull: Process Understanding of Transamination Reaction in Chiral Pharmaceutical Intermediate Production Catalyzed by an Engineered Amine Transaminase. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Perçin, Zeynep – PersonEntity: Name: NameFull: Kleinbeck, Florian – PersonEntity: Name: NameFull: Bubenheim, Paul – PersonEntity: Name: NameFull: Ruch, Thomas – PersonEntity: Name: NameFull: Liese, Andreas IsPartOfRelationships: – BibEntity: Dates: – D: 17 M: 02 Text: 2/17/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 18673880 Numbering: – Type: volume Value: 17 – Type: issue Value: 4 Titles: – TitleFull: ChemCatChem Type: main |
| ResultId | 1 |
