Asymmetric catalysis by flavin-dependent halogenases.
atroposelective
desymmetrization
halocyclization
halogenase
kinetic resolution
Journal
Chirality
ISSN: 1520-636X
Titre abrégé: Chirality
Pays: United States
ID NLM: 8914261
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
15
02
2023
received:
22
12
2022
accepted:
16
02
2023
medline:
12
7
2023
pubmed:
15
3
2023
entrez:
14
3
2023
Statut:
ppublish
Résumé
In nature, flavin-dependent halogenases (FDHs) catalyze site-selective chlorination and bromination of aromatic natural products. This ability has led to extensive efforts to engineer FDHs for selective chlorination, bromination, and iodination of electron rich aromatic compounds. On the other hand, FDHs are unique among halogenases and haloperoxidases that exhibit catalyst-controlled site selectivity in that no examples of enantioselective FDH catalysis in natural product biosynthesis have been characterized. Over the past several years, our group has established that FDHs can catalyze enantioselective reactions involving desymmetrization, atroposelective halogenation, and halocyclization. Achieving high activity and selectivity for these reactions has required extensive mutagenesis and mitigation of problems resulting from hypohalous acid generated during FDH catalysis. The single-component flavin reductase/FDH AetF is unique among the wild type enzyme we have studied in that it provides high activity and selectivity toward several asymmetric transformations. These results highlight the ability of FDH active sites to tolerate different substrate topologies and suggest that they could be useful for a broad range of oxidative halogenations.
Substances chimiques
Flavins
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
452-460Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM115665
Pays : United States
Organisme : NIH HHS
ID : R01 GM115665
Pays : United States
Informations de copyright
© 2023 The Authors. Chirality published by Wiley Periodicals LLC.
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