Resistance gene-guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases.
biosynthesis
genome mining
natural products
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
medline:
22
11
2023
pubmed:
20
11
2023
entrez:
20
11
2023
Statut:
ppublish
Résumé
With the significant increase in the availability of microbial genome sequences in recent years, resistance gene-guided genome mining has emerged as a powerful approach for identifying natural products with specific bioactivities. Here, we present the use of this approach to reveal the roseopurpurins as potent inhibitors of cyclin-dependent kinases (CDKs), a class of cell cycle regulators implicated in multiple cancers. We identified a biosynthetic gene cluster (BGC) with a putative resistance gene with homology to human CDK2. Using targeted gene disruption and transcription factor overexpression in
Identifiants
pubmed: 37983497
doi: 10.1073/pnas.2310522120
pmc: PMC10691236
doi:
Substances chimiques
Cyclin-Dependent Kinases
EC 2.7.11.22
Cyclin-Dependent Kinase 2
EC 2.7.11.22
Cyclins
0
Enzyme Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2310522120Déclaration de conflit d'intérêts
Competing interests statement:K.L.D, B.P., N.L., D.M., A.C., Y.-M.C., L.H., M.N., J.P., H.L.N. and C.J.B.H. are all shareholders in Hexagon Bio.
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