A reinvestigation of the acetone extract of the strain CA-091830 of Streptomyces canus, producer of the imipenem potentiator krisynomycin, resulted in the isolation of two additional analogues, krisynomycins B (1) and C (2), with different chlorination patterns. Genome sequencing of the strain followed by detailed bioinformatics analysis led to the identification of the corresponding biosynthetic gene cluster (BGC) of this cyclic nonribosomal peptide family. The planar structure of the new molecules was determined using HRMS, ESI-qTOF-MS/MS, and 1D and 2D NMR data. Their absolute configuration was proposed using a combination of Marfey’s and bioinformatic BGC analyses. The krisynomycins displayed weak to negligible antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA), which was significantly enhanced when tested in combination with sublethal concentrations of imipenem. The halogenation pattern plays a key role in the antimicrobial activity and imipenem-potentiating effects of the compounds, with molecules having a higher number of chlorine atoms potentiating the effect of imipenem at lower doses.

中文翻译：

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Krisynomycins，亚胺培南增效剂，对抗耐甲氧西林金黄色葡萄球菌，由 Streptomyces canus 产生。

对Streptomyces canus菌株 CA-091830 的丙酮提取物进行再研究，该菌株是亚胺培南增效剂 krisynomycin 的生产者，结果分离出两种额外的类似物，krisynomycins B ( 1 ) 和 C ( 2 ))，具有不同的氯化模式。对该菌株进行基因组测序，然后进行详细的生物信息学分析，从而确定了该环状非核糖体肽家族的相应生物合成基因簇 (BGC)。使用 HRMS、ESI-qTOF-MS/MS 以及 1D 和 2D NMR 数据确定了新分子的平面结构。它们的绝对配置是使用 Marfey 和生物信息学 BGC 分析的组合提出的。krisynomycins 对耐甲氧西林金黄色葡萄球菌表现出微弱甚至可以忽略不计的抗生素活性(MRSA)，当与亚致死浓度的亚胺培南联合测试时显着增强。卤化模式在化合物的抗微生物活性和亚胺培南增强作用中起关键作用，具有较高氯原子数的分子在较低剂量下增强亚胺培南的作用。