Flexizyme-Enabled Benchtop Biosynthesis of Thiopeptides.
Journal
Journal of the American Chemical Society
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056
Informations de publication
Date de publication:
16 01 2019
16 01 2019
Historique:
pubmed:
3
1
2019
medline:
4
6
2020
entrez:
3
1
2019
Statut:
ppublish
Résumé
Thiopeptides are natural antibiotics that are fashioned from short peptides by multiple layers of post-translational modification. Their biosynthesis, in particular the pyridine synthases that form the macrocyclic antibiotic core, has attracted intensive research but is complicated by the challenges of reconstituting multiple-pathway enzymes. By combining select RiPP enzymes with cell free expression and flexizyme-based codon reprogramming, we have developed a benchtop biosynthesis of thiopeptide scaffolds. This strategy side-steps several challenges related to the investigation of thiopeptide enzymes and allows access to analytical quantities of new thiopeptide analogs. We further demonstrate that this strategy can be used to validate the activity of new pyridine synthases without the need to reconstitute the cognate prior pathway enzymes.
Identifiants
pubmed: 30602112
doi: 10.1021/jacs.8b11521
pmc: PMC6642631
mid: NIHMS1040879
doi:
Substances chimiques
Anti-Bacterial Agents
0
Aptamers, Nucleotide
0
Peptides, Cyclic
0
RNA, Catalytic
0
Thiazoles
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
758-762Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM125005
Pays : United States
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