Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation
Heterocycles are important building blocks in pharmaceutical drugs and their enzymatic synthesis is attracting increasing interest. In recent years, various enzymes of the amidohydrolase superfamily were reported to catalyze heterocycle-forming condensation reactions. One of these enzymes, MxcM, is...
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MDPI AG
2021-07-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/11/8/892 |
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| author | Lea Winand Dustin Joshua Vollmann Jacqueline Hentschel Markus Nett |
| author_facet | Lea Winand Dustin Joshua Vollmann Jacqueline Hentschel Markus Nett |
| author_sort | Lea Winand |
| collection | DOAJ |
| description | Heterocycles are important building blocks in pharmaceutical drugs and their enzymatic synthesis is attracting increasing interest. In recent years, various enzymes of the amidohydrolase superfamily were reported to catalyze heterocycle-forming condensation reactions. One of these enzymes, MxcM, is biochemically and kinetically characterized in this study. MxcM generates an imidazoline moiety in the biosynthesis of the natural product pseudochelin A, which features potent anti-inflammatory properties. The enzyme shows maximal activity at 50 °C and pH 10 as well as a <i>k<sub>cat</sub>/K<sub>m</sub></i> value of 22,932 s<sup>−1</sup> M<sup>−1</sup> at its temperature optimum. Experimental data suggest that the activity of MxcM does not depend on a catalytic metal ion, which is uncommon among amidohydrolases. MxcM is highly active in diverse organic solvents and concentrated salt solutions. Furthermore, we show that MxcM is also capable to introduce imidazoline rings into derivatives of its natural substrate myxochelin B. Overall, MxcM is a solvent-stable, halotolerant enzyme with promising biochemical and kinetic properties and, in future, might become a valuable biocatalyst for the manufacturing of pharmaceutical drugs. |
| first_indexed | 2024-03-10T08:56:52Z |
| format | Article |
| id | doaj.art-d029cfe347ba49b78058747e932ca238 |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-10T08:56:52Z |
| publishDate | 2021-07-01 |
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| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-d029cfe347ba49b78058747e932ca2382023-11-22T07:06:20ZengMDPI AGCatalysts2073-43442021-07-0111889210.3390/catal11080892Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle FormationLea Winand0Dustin Joshua Vollmann1Jacqueline Hentschel2Markus Nett3Department of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Str. 66, 44227 Dortmund, GermanyDepartment of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Str. 66, 44227 Dortmund, GermanyDepartment of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Str. 66, 44227 Dortmund, GermanyDepartment of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Str. 66, 44227 Dortmund, GermanyHeterocycles are important building blocks in pharmaceutical drugs and their enzymatic synthesis is attracting increasing interest. In recent years, various enzymes of the amidohydrolase superfamily were reported to catalyze heterocycle-forming condensation reactions. One of these enzymes, MxcM, is biochemically and kinetically characterized in this study. MxcM generates an imidazoline moiety in the biosynthesis of the natural product pseudochelin A, which features potent anti-inflammatory properties. The enzyme shows maximal activity at 50 °C and pH 10 as well as a <i>k<sub>cat</sub>/K<sub>m</sub></i> value of 22,932 s<sup>−1</sup> M<sup>−1</sup> at its temperature optimum. Experimental data suggest that the activity of MxcM does not depend on a catalytic metal ion, which is uncommon among amidohydrolases. MxcM is highly active in diverse organic solvents and concentrated salt solutions. Furthermore, we show that MxcM is also capable to introduce imidazoline rings into derivatives of its natural substrate myxochelin B. Overall, MxcM is a solvent-stable, halotolerant enzyme with promising biochemical and kinetic properties and, in future, might become a valuable biocatalyst for the manufacturing of pharmaceutical drugs.https://www.mdpi.com/2073-4344/11/8/892amidohydrolasebiocatalysisheterocycleimidazolineMxcMnatural product |
| spellingShingle | Lea Winand Dustin Joshua Vollmann Jacqueline Hentschel Markus Nett Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation Catalysts amidohydrolase biocatalysis heterocycle imidazoline MxcM natural product |
| title | Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation |
| title_full | Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation |
| title_fullStr | Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation |
| title_full_unstemmed | Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation |
| title_short | Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation |
| title_sort | characterization of a solvent tolerant amidohydrolase involved in natural product heterocycle formation |
| topic | amidohydrolase biocatalysis heterocycle imidazoline MxcM natural product |
| url | https://www.mdpi.com/2073-4344/11/8/892 |
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