Genome-Driven Discovery of Hygrocins in Streptomyces rapamycinicus .
Manar Magdy Mahmoud MohamedZhijie YangKah Yean LumGundela PeschelMiriam A RosenbaumTilmann WeberSonia CorianiCharlotte Held GotfredsenLing DingPublished in: Journal of natural products (2024)
Ansamycins, represented by the antituberculosis drug rifamycin, are an important family of natural products. To obtain new ansamycins, Streptomyces rapamycinicus IMET 43975 harboring an ansamycin biosynthetic gene cluster was fermented in a 50 L scale, and subsequent purification work led to the isolation of five known and four new analogues, where hygrocin W ( 2 ) belongs to benzoquinonoid ansamycins, and the other three hygrocins, hygrocins X-Z ( 6 - 8 ), are new seco-hygrocins. The structures of ansamycins ( 1 - 8 ) were determined by the analysis of spectroscopic (1D/2D NMR and ECD) and MS spectrometric data. The Baeyer-Villiger enzyme which catalyzed the ester formation in the ansa-ring was confirmed through in vivo CRISPR base editing. The discovery of these compounds further enriches the structural diversity of ansamycins.
Keyphrases
- crispr cas
- genome wide
- molecular docking
- small molecule
- genome editing
- high resolution
- high throughput
- mass spectrometry
- magnetic resonance
- dna methylation
- electronic health record
- copy number
- multiple sclerosis
- liquid chromatography
- ms ms
- big data
- room temperature
- solid state
- gas chromatography
- adverse drug
- single cell
- transcription factor
- artificial intelligence