Expanding the Chemical Diversity of Grisechelins via Heterologous Expression.

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 ).