Alwali Amir Y, Santos Diane, Aguilar César, Birch Audrey, Rodriguez-Orduña Lorena, Roberts Carson B, Modi Ramya, Licona-Cassani Cuauhtemoc, Parkinson Elizabeth I
D epartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Centro de Biotecnología FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, 64849 Monterrey, México.
J Ind Microbiol Biotechnol. 2024 Jan 9;51. doi: 10.1093/jimb/kuae014.
Narrow-spectrum antibiotics are of great interest given their ability to spare the microbiome and decrease widespread antibiotic resistance compared to broad-spectrum antibiotics. Herein, we screened an in-house library of Actinobacteria strains for selective activity against Acinetobacter baumannii and successfully identified Streptomyces sp. CS-62 as a producer of a natural product with this valuable activity. Analysis of the cultures via high-resolution mass spectrometry and tandem mass spectrometry, followed by comparison with molecules in the Natural Product Atlas and the Global Natural Products Social Molecular Networking platform, suggested a novel natural product. Genome mining analysis initially supported the production of a novel kirromycin derivative. Isolation and structure elucidation via mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses revealed that the active natural product was the known natural product factumycin, exposing omissions and errors in the consulted databases. While public databases are generally very useful for avoiding rediscovery of known molecules, rediscovery remains a problem due to public databases either being incomplete or having errors that result in failed dereplication. Overall, the work describes the ongoing problem of dereplication and the continued need for public database curation.
鉴于窄谱抗生素相较于广谱抗生素具有保护微生物群并降低广泛抗生素耐药性的能力,它们备受关注。在此,我们筛选了一个放线菌菌株的内部文库,以寻找对鲍曼不动杆菌具有选择性活性的菌株,并成功鉴定出链霉菌属CS-62是一种具有这种宝贵活性的天然产物的产生菌。通过高分辨率质谱和串联质谱对培养物进行分析,然后与天然产物图谱和全球天然产物社会分子网络平台中的分子进行比较,表明这是一种新型天然产物。基因组挖掘分析最初支持一种新型奇霉素衍生物的产生。通过质谱和核磁共振(NMR)分析进行分离和结构解析,结果表明活性天然产物是已知的天然产物法克霉素,这揭示了所查询数据库中的遗漏和错误。虽然公共数据库通常对于避免重新发现已知分子非常有用,但由于公共数据库不完整或存在导致重复数据去除失败的错误,重新发现仍然是一个问题。总体而言,这项工作描述了重复数据去除中持续存在的问题以及对公共数据库管理的持续需求。