Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, China.
Nat Commun. 2022 Sep 2;13(1):5169. doi: 10.1038/s41467-022-32901-0.
Medermycin, produced by Streptomyces species, represents a family of antibiotics with significant activity against Gram-positive pathogens. The biosynthesis of this family of natural products has been studied, and new skeletons related to medermycin have rarely been reported until recently. Herein, we report eight chimeric medermycin-type natural products with unusual polycyclic skeletons. The formation of these compounds features some key nonenzymatic steps, which inspired us to construct complex polycyclic skeletons via three efficient one-step reactions under mild conditions. This strategy was further developed to efficiently synthesize analogues for biological activity studies. The synthetic compounds, chimedermycins L and M, and sekgranaticin B, show potent antibacterial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis. This work paves the way for understanding the nonenzymatic formation of complex natural products and using it to synthesize natural product derivatives.
美替麦星由链霉菌属产生，是一类对革兰氏阳性病原体具有显著活性的抗生素。该家族天然产物的生物合成已被研究，直到最近才很少有新的与美替麦星相关的骨架被报道。在此，我们报告了 8 种具有不寻常多环骨架的嵌合美替麦星型天然产物。这些化合物的形成具有一些关键的非酶步骤，这启发我们在温和条件下通过三个高效的一步反应构建复杂的多环骨架。该策略进一步发展为有效合成用于生物活性研究的类似物。合成化合物 chimedermycins L 和 M 以及 sekgranaticin B 对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌和耐甲氧西林表皮葡萄球菌具有很强的抗菌活性。这项工作为理解复杂天然产物的非酶形成以及利用它来合成天然产物衍生物铺平了道路。
