A refined picture of the native amine dehydrogenase family revealed by extensive biodiversity screening.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 Jun 2024
10 Jun 2024
Historique:
received:
21
09
2023
accepted:
20
05
2024
medline:
11
6
2024
pubmed:
11
6
2024
entrez:
10
6
2024
Statut:
epublish
Résumé
Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.
Identifiants
pubmed: 38858403
doi: 10.1038/s41467-024-49009-2
pii: 10.1038/s41467-024-49009-2
doi:
Substances chimiques
Amines
0
Oxidoreductases Acting on CH-NH Group Donors
EC 1.5.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4933Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-21-ESRE-0021
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-19-CE07-0007
Informations de copyright
© 2024. The Author(s).
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