Kaur Amninder, Guerrero-Garzón Jaime Felipe, Rasheed Sari, Zehl Martin, Fries Franziska, Morgenstern Bernd, Zotchev Sergey B, Müller Rolf
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), PharmaScienceHub (PSH), Saarland University Campus, 66123, Saarbrücken, Germany.
German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124, Braunschweig, Germany.
Angew Chem Int Ed Engl. 2025 Jun 17;64(25):e202425588. doi: 10.1002/anie.202425588. Epub 2025 Apr 25.
A member of a new family of glycopeptides, named saarvienin A, was isolated from a rare actinomycete Amycolatopsis sp. YIM10. Extensive NMR and MS analyses revealed a halogenated peptide core comprising four amino acids cyclized via a ureido linkage with an exocyclic 2-hydroxy-3-(4-hydroxyphenyl)propyl residue connected to a five-sugar/aminosugar chain. Two of the three aminosugars constitute the N-methylated and N,O-dimethylated derivatives of eremosamine (4-epi-vancosamine) that have not been reported in any natural product. Saarvienin A exhibits potent activity against a range of Gram-positive bacteria, effectively overcoming resistance to several frontline antibiotics in clinical isolates. It demonstrates an eight-fold reduction in minimum inhibitory concentrations (MICs) against methicillin-resistant, vancomycin-intermediate, and daptomycin-resistant Staphylococcus aureus compared to vancomycin.
从一种罕见的放线菌拟无枝酸菌属Amycolatopsis sp. YIM10中分离出一种新的糖肽家族成员，命名为萨尔维宁A。广泛的核磁共振（NMR）和质谱（MS）分析表明，其卤化肽核心由四个氨基酸通过脲基连接环化而成，带有一个与五糖/氨基糖链相连的环外2-羟基-3-(4-羟基苯基)丙基残基。三种氨基糖中的两种构成了埃雷莫胺（4-表万古糖胺）的N-甲基化和N,O-二甲基化衍生物，这在任何天然产物中均未报道过。萨尔维宁A对一系列革兰氏阳性菌表现出强大活性，有效克服了临床分离株对几种一线抗生素的耐药性。与万古霉素相比，它对耐甲氧西林、万古霉素中介和耐达托霉素的金黄色葡萄球菌的最低抑菌浓度（MIC）降低了八倍。
