Dynamic modulation of enzyme activity by synthetic CRISPR-Cas6 endonucleases.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
23
06
2021
accepted:
25
02
2022
pubmed:
27
4
2022
medline:
3
5
2022
entrez:
26
4
2022
Statut:
ppublish
Résumé
In nature, dynamic interactions between enzymes play a crucial role in defining cellular metabolism. By controlling the spatial and temporal organization of these supramolecular complexes called metabolons, natural metabolism can be tuned in a highly dynamic manner. Here, we repurpose the CRISPR-Cas6 family proteins as a synthetic strategy to create dynamic metabolons by combining the ease of RNA processing and the predictability of RNA hybridization for protein assembly. By disturbing RNA-RNA networks using toehold-mediated strand displacement reactions, on-demand assembly and disassembly are achieved using both synthetic RNA triggers and mCherry messenger RNA. Both direct and 'Turn-On' assembly of the pathway enzymes tryptophan-2-monooxygenase and indoleacetamide hydrolase can enhance indole-3-acetic acid production by up to ninefold. Even multimeric enzymes can be assembled to improve malate production by threefold. By interfacing with endogenous mRNAs, more complex metabolons may be constructed, resulting in a self-responsive metabolic machinery capable of adapting to changing cellular demand.
Identifiants
pubmed: 35468950
doi: 10.1038/s41589-022-01005-7
pii: 10.1038/s41589-022-01005-7
doi:
Substances chimiques
RNA
63231-63-0
Endonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
492-500Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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