Cupin-Type Dimethylsulfoniopropionate Lyase from Pelagibacter ubique (DddKPu) Catalyzes Aza-Michael Addition of Primary and Secondary Amines to Acrylic Acid
The formation of carbon─nitrogen (C─N) bonds is a cornerstone of organic synthesis, underpinning the production of amines, imines, and nitriles found in numerous active ingredients. Among the methods for C─N bond formation, the aza-Michael addition stands out as a powerful and versatile approach. He...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/400915 |
| Acceso en línea: | http://hdl.handle.net/10261/400915 https://api.elsevier.com/content/abstract/scopus_id/105016202170 |
| Access Level: | acceso abierto |
| Palabra clave: | Dimethylsulfoniopropionate lyase Acrylate Aza‐Michael addition Biocatalysis http://metadata.un.org/sdg/3 Ensure healthy lives and promote well-being for all at all ages |
| Sumario: | The formation of carbon─nitrogen (C─N) bonds is a cornerstone of organic synthesis, underpinning the production of amines, imines, and nitriles found in numerous active ingredients. Among the methods for C─N bond formation, the aza-Michael addition stands out as a powerful and versatile approach. Herein, we present a biocatalytic strategy for the efficient aza-Michael addition of primary and secondary amines to acrylic acid, i.e., aza-Michaelase activity, leveraging the promiscuity of dimethylsulfoniopropionate (DMSP) lyase from Pelagibacter ubique HTCC1062 (DddKPu). In vivo DddKPu catalyzes the β-elimination of DMSP to sodium acrylate and dimethylsulfide (i.e., a retro sulfa-Michael reaction). Here, we screened DddKPu against a diverse library of 30 primary and 44 secondary amines. The wild-type enzyme achieved 90%-100% conversion and 40%-86% isolated yields of N,N-disubstituted-β-amino acids with secondary amines. For primary amines, the W26G variant proved optimal, furnishing 50%-100% conversion and 43%-81% isolated yields of N-substituted-β-amino acids. Notably, the enzyme exhibited remarkable chemoselectivity: for pyrrolidin-2-ylmethanamine, the reaction occurred exclusively at the secondary amine, while for piperidin-2-ylmethanamine, it reacted selectively at the primary amine. These findings highlight DddKPu as a versatile biocatalyst for the selective synthesis of β-amino acids, expanding the toolbox for C─N bond formation. |
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