Oliver Ryan A, Li Rongfeng, Townsend Craig A
Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland, USA.
Nat Chem Biol. 2018 Jan;14(1):5-7. doi: 10.1038/nchembio.2526. Epub 2017 Nov 20.
The N-sulfonated monocyclic β-lactam ring characteristic of the monobactams confers resistance to zinc metallo-β-lactamases and affords the most effective class to combat carbapenem-resistant enterobacteria (CRE). Here we report unprecedented nonribosomal peptide synthetase activities, wherein an assembled tripeptide is N-sulfonated in trans before direct synthesis of the β-lactam ring in a noncanonical, cysteine-containing thioesterase domain. This means of azetidinone synthesis is distinct from the three others known in nature.
单环β-内酰胺类抗生素的N-磺化单环β-内酰胺环结构使其对锌金属β-内酰胺酶具有抗性，是对抗耐碳青霉烯类肠杆菌（CRE）最有效的一类药物。在此，我们报道了前所未有的非核糖体肽合成酶活性，即一个组装好的三肽在非典型的含半胱氨酸硫酯酶结构域中直接合成β-内酰胺环之前先进行反式N-磺化。这种氮杂环丁酮的合成方式与自然界已知的其他三种方式不同。
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