Enzymatic synthesis of mono- and trifluorinated alanine enantiomers expands the scope of fluorine biocatalysis.


Journal

Communications chemistry
ISSN: 2399-3669
Titre abrégé: Commun Chem
Pays: England
ID NLM: 101725670

Informations de publication

Date de publication:
09 May 2024
Historique:
received: 28 11 2023
accepted: 24 04 2024
medline: 10 5 2024
pubmed: 10 5 2024
entrez: 9 5 2024
Statut: epublish

Résumé

Fluorinated amino acids serve as an entry point for establishing new-to-Nature chemistries in biological systems, and novel methods are needed for the selective synthesis of these building blocks. In this study, we focused on the enzymatic synthesis of fluorinated alanine enantiomers to expand fluorine biocatalysis. The alanine dehydrogenase from Vibrio proteolyticus and the diaminopimelate dehydrogenase from Symbiobacterium thermophilum were selected for in vitro production of (R)-3-fluoroalanine and (S)-3-fluoroalanine, respectively, using 3-fluoropyruvate as the substrate. Additionally, we discovered that an alanine racemase from Streptomyces lavendulae, originally selected for setting an alternative enzymatic cascade leading to the production of these non-canonical amino acids, had an unprecedented catalytic efficiency in β-elimination of fluorine from the monosubstituted fluoroalanine. The in vitro enzymatic cascade based on the dehydrogenases of V. proteolyticus and S. thermophilum included a cofactor recycling system, whereby a formate dehydrogenase from Pseudomonas sp. 101 (either native or engineered) coupled formate oxidation to NAD(P)H formation. Under these conditions, the reaction yields for (R)-3-fluoroalanine and (S)-3-fluoroalanine reached >85% on the fluorinated substrate and proceeded with complete enantiomeric excess. The selected dehydrogenases also catalyzed the conversion of trifluoropyruvate into trifluorinated alanine as a first-case example of fluorine biocatalysis with amino acids carrying a trifluoromethyl group.

Identifiants

pubmed: 38724655
doi: 10.1038/s42004-024-01188-1
pii: 10.1038/s42004-024-01188-1
doi:

Types de publication

Journal Article

Langues

eng

Pagination

104

Subventions

Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 713683
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 814418
Organisme : Villum Fonden (Villum Foundation)
ID : 40979
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF10CC1016517
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF18CC0033664

Informations de copyright

© 2024. The Author(s).

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Auteurs

Manuel Nieto-Domínguez (M)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.

Aboubakar Sako (A)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.

Kasper Enemark-Rasmussen (K)

Department of Chemistry, NMR Center, Technical University of Denmark, Kongens Lyngby, Denmark.

Charlotte Held Gotfredsen (CH)

Department of Chemistry, NMR Center, Technical University of Denmark, Kongens Lyngby, Denmark.

Daniela Rago (D)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.

Pablo I Nikel (PI)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark. pabnik@biosustain.dtu.dk.

Classifications MeSH