Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, PR China.
J Antibiot (Tokyo). 2024 Aug;77(8):506-514. doi: 10.1038/s41429-024-00736-0. Epub 2024 May 14.
Four new echinomycin congeners, quinomycins M-P (1-4) were isolated from the cultures of the soil-derived Streptomyces sp. CPCC205575. The planar structures were determined by comprehensive analyses of NMR and HRESIMS/MS data. The absolute configurations were elucidated by the advanced Marfey's method combined with biosynthetic gene analysis. Compounds 1-4 represent the first examples of quinomycin-type natural products with the sulfur atom at the N,S-dimethylcysteine residue oxidized as a sulfoxide group forming the unusual N-methyl-3-methylsulfinyl-alanine residue. Bioassay results revealed that the oxidation of the sulfur atom at the Cys or Cys' residues led to dramatic decrease of cytotoxicity and antimicrobial activity.
从土壤来源的链霉菌 CPCC205575 的培养物中分离得到了四个新的埃希霉素同系物，醌霉素 M-P（1-4）。通过 NMR 和 HRESIMS/MS 数据分析的综合分析确定了其平面结构。通过先进的 Marfey 法结合生物合成基因分析阐明了绝对构型。化合物 1-4 代表了第一个具有 N，S-二甲基半胱氨酸残基上的硫原子氧化为亚砜基形成不寻常的 N-甲基-3-甲基亚磺酰基丙氨酸残基的醌霉素型天然产物的例子。生物测定结果表明，Cys 或 Cys'残基上的硫原子氧化导致细胞毒性和抗菌活性显著降低。
