Borrelidin B: isolation, biological activity, and implications for nitrile biosynthesis.
J Nat Prod
; 77(11): 2570-4, 2014 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-25393949
ABSTRACT
Borrelidin (1) is a nitrile-containing bacterially derived polyketide that is a potent inhibitor of bacterial and eukaryotic threonyl-tRNA synthetases. We now report the discovery of borrelidin B (2), a tetrahydro-borrelidin derivative containing an aminomethyl group in place of the nitrile functionality in borrelidin. The discovery of this new metabolite has implications for both the biosynthesis of the nitrile group and the bioactivity of the borrelidin compound class. Screening in the SToPS assay for tRNA synthetase inhibition revealed that the nitrile moiety is essential for activity, while profiling using our in-house image-based cytological profiling assay demonstrated that 2 retains biological activity by causing a mitotic stall, even in the absence of the nitrile motif.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Treonina-tRNA Ligase
/
Nitrilas
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article