Casella Vincenza, Della Sala Gerardo, Scarpato Silvia, Buonocore Carmine, Ragozzino Costanza, Tedesco Pietro, Coppola Daniela, Vitale Giovanni Andrea, de Pascale Donatella, Palma Esposito Fortunato
Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, Italy.
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres, 31, 98166 Messina, Italy.
Mar Drugs. 2025 Jan 14;23(1):41. doi: 10.3390/md23010041.
With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant strains and other Gram-positive pathogens, including the foodborne pathogen . Finally, in silico analysis of BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase.
随着对抗菌素耐药性的日益关注，确定针对多重耐药细菌的新先导化合物至关重要。本研究采用快速小型化筛选方法，同时培养和评估约300株海洋菌株的生物表面活性剂和抗菌活性，从而筛选出深海菌株BCP32。串联质谱分子网络与生物测定导向分馏相结合，揭示该菌株是表面活性素和诺比酰胺的高产工厂。特别是，在细菌胞外代谢组中鉴定出84种诺比酰胺同系物，其中71种为新代谢物。从中分离出四种主要化合物，包括已知的TL-119和诺比酰胺I，以及两种新的诺比酰胺T1和S1。TL-119和诺比酰胺S1对各种多重耐药菌株和其他革兰氏阳性病原体，包括食源性病原体，表现出强大的抗生素活性。最后，对BCP32基因组的计算机分析表明，诺比酰胺的生物合成由一种以前未知的七模块非核糖体肽合成酶指导。
