ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine
The pivotal role played by ω-transaminases (ω-TAs) in the synthesis of chiral amines used as building blocks for drugs and pharmaceuticals is widely recognized. However, chiral bulky amines are challenging to produce. Herein, a ω-TA (TR<sub>8</sub>) from a marine bacterium was used to sy...
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MDPI AG
2021-02-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/11/3/307 |
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| author | Carlos J. C. Rodrigues Manuel Ferrer Carla C. C. R. de Carvalho |
| author_facet | Carlos J. C. Rodrigues Manuel Ferrer Carla C. C. R. de Carvalho |
| author_sort | Carlos J. C. Rodrigues |
| collection | DOAJ |
| description | The pivotal role played by ω-transaminases (ω-TAs) in the synthesis of chiral amines used as building blocks for drugs and pharmaceuticals is widely recognized. However, chiral bulky amines are challenging to produce. Herein, a ω-TA (TR<sub>8</sub>) from a marine bacterium was used to synthesize a fluorine chiral amine from a bulky ketone. An analysis of the reaction conditions for process development showed that isopropylamine concentrations above 75 mM had an inhibitory effect on the enzyme. Five different organic solvents were investigated as co-solvents for the ketone (the amine acceptor), among which 25–30% (<i>v</i>/<i>v</i>) dimethyl sulfoxide (DMSO) produced the highest enzyme activity. The reaction reached equilibrium after 18 h at 30% of conversion. An in situ product removal (ISPR) approach using an aqueous organic two-phase system was tested to mitigate product inhibition. However, the enzyme activity initially decreased because the ketone substrate preferentially partitioned into the organic phase, <i>n</i>-hexadecane. Consequently, DMSO was added to the system to increase substrate mass transfer without affecting the ability of the organic phase to prevent inhibition of the enzyme activity by the product. Thus, the enzyme reaction was maintained, and the product amount was increased for a 62 h reaction time. The investigated ω-TA can be used in the bioconversion of bulky ketones to chiral amines for future bioprocess applications. |
| first_indexed | 2024-03-09T00:30:46Z |
| format | Article |
| id | doaj.art-add0dd79bf3b426aa0ccf0d085866939 |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-09T00:30:46Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-add0dd79bf3b426aa0ccf0d0858669392023-12-11T18:31:46ZengMDPI AGCatalysts2073-43442021-02-0111330710.3390/catal11030307ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)EthylamineCarlos J. C. Rodrigues0Manuel Ferrer1Carla C. C. R. de Carvalho2iBB-Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, PortugalInstitute of Catalysis, Consejo Superior de Investigaciones Científicas, 28049 Madrid, SpainiBB-Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, PortugalThe pivotal role played by ω-transaminases (ω-TAs) in the synthesis of chiral amines used as building blocks for drugs and pharmaceuticals is widely recognized. However, chiral bulky amines are challenging to produce. Herein, a ω-TA (TR<sub>8</sub>) from a marine bacterium was used to synthesize a fluorine chiral amine from a bulky ketone. An analysis of the reaction conditions for process development showed that isopropylamine concentrations above 75 mM had an inhibitory effect on the enzyme. Five different organic solvents were investigated as co-solvents for the ketone (the amine acceptor), among which 25–30% (<i>v</i>/<i>v</i>) dimethyl sulfoxide (DMSO) produced the highest enzyme activity. The reaction reached equilibrium after 18 h at 30% of conversion. An in situ product removal (ISPR) approach using an aqueous organic two-phase system was tested to mitigate product inhibition. However, the enzyme activity initially decreased because the ketone substrate preferentially partitioned into the organic phase, <i>n</i>-hexadecane. Consequently, DMSO was added to the system to increase substrate mass transfer without affecting the ability of the organic phase to prevent inhibition of the enzyme activity by the product. Thus, the enzyme reaction was maintained, and the product amount was increased for a 62 h reaction time. The investigated ω-TA can be used in the bioconversion of bulky ketones to chiral amines for future bioprocess applications.https://www.mdpi.com/2073-4344/11/3/307omega-transaminasebioconversionbulky ketonefluorine aminechiral aminemarine biocatalyst |
| spellingShingle | Carlos J. C. Rodrigues Manuel Ferrer Carla C. C. R. de Carvalho ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine Catalysts omega-transaminase bioconversion bulky ketone fluorine amine chiral amine marine biocatalyst |
| title | ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine |
| title_full | ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine |
| title_fullStr | ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine |
| title_full_unstemmed | ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine |
| title_short | ω-Transaminase-Mediated Asymmetric Synthesis of (<i>S</i>)-1-(4-Trifluoromethylphenyl)Ethylamine |
| title_sort | ω transaminase mediated asymmetric synthesis of i s i 1 4 trifluoromethylphenyl ethylamine |
| topic | omega-transaminase bioconversion bulky ketone fluorine amine chiral amine marine biocatalyst |
| url | https://www.mdpi.com/2073-4344/11/3/307 |
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