Expanding the Chemical Diversity of Grisechelins via Heterologous Expression.
J Nat Prod
; 87(2): 371-380, 2024 02 23.
Article
en En
| MEDLINE
| ID: mdl-38301035
ABSTRACT
Thiazole scaffold-based small molecules exhibit a range of biological activities and play important roles in drug discovery. Based on bioinformatics analysis, a putative biosynthetic gene cluster (BGC) for thiazole-containing compounds was identified from Streptomyces sp. SCSIO 40020. Heterologous expression of this BGC led to the production of eight new thiazole-containing compounds, grisechelins E, F, and I-N (1, 2, 5-10), and two quinoline derivatives, grisechelins G and H (3 and 4). The structures of 1-10, including their absolute configurations, were elucidated by HRESIMS, NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction analysis. Grisechelin F (2) is a unique derivative, distinguished by the presence of a salicylic acid moiety. The biosynthetic pathway for 2 was proposed based on bioinformatics analysis and in vivo gene knockout experiments. Grisechelin E (1) displayed moderate antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MIC of 8 µg mL-1).
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Streptomyces
Idioma:
En
Revista:
J Nat Prod
Año:
2024
Tipo del documento:
Article