Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy , Ocean University of China , Qingdao 266003 , People's Republic of China.
Laboratory for Marine Drugs and Bioproducts , Qingdao National Laboratory for Marine Science and Technology , Qingdao 266200 , People's Republic of China.
J Org Chem. 2019 Feb 1;84(3):1228-1237. doi: 10.1021/acs.joc.8b02614. Epub 2019 Jan 16.
A challenging problem in natural product discovery is to rapidly dereplicate known compounds and expose novel ones from complicated components. Herein, integrating the LC-MS/MS-dependent molecular networking and H NMR techniques efficiently and successfully enabled the targeted identification of seven new cyclohexadepsipeptides, chrysogeamides A-G (1-7), from the coral-derived fungus Penicillium chrysogenum (CHNSCLM-0003) which was targeted from a library of marine-derived Penicillium fungi. Compound 4 features a rare 3-hydroxy-4-methylhexanoic acid (HMHA) moiety which was first discovered from marine-derived organisms. Interestingly, isotope-labeling feeding experiments confirmed that C-l-Leu was transformed into C-d-Leu moiety, indicating that d-Leu could be isomerized from l-Leu. Compounds 1 and 2 obviously promoted angiogenesis in zebrafish at 1.0 μg/mL with nontoxic to embryonic zebrafish at 100 μg/mL. Combining molecular networking with H NMR as a discovery tool will be implemented as a systematic strategy, not only for known compounds dereplication but also for untapped reservoir discovery.
在天然产物发现中，一个具有挑战性的问题是快速去除已知化合物的复制品，并从复杂的成分中暴露新的化合物。本文中，整合基于 LC-MS/MS 的分子网络和 1 H NMR 技术，有效地、成功地实现了从海洋来源的青霉真菌文库中靶向分离的珊瑚来源真菌拟青霉（CHNSCLM-0003）中七种新的环己二肽，即 Chrysogeamide A-G（1-7）的靶向鉴定。化合物 4 具有罕见的 3-羟基-4-甲基己酸（HMHA）部分，这是首次从海洋来源的生物中发现的。有趣的是，同位素标记喂养实验证实 C-l-Leu 被转化为 C-d-Leu 部分，表明 d-Leu 可以从 l-Leu 异构化而来。化合物 1 和 2 在 1.0 μg/mL 浓度下明显促进斑马鱼的血管生成，而在 100 μg/mL 浓度下对胚胎斑马鱼没有毒性。将分子网络与 1 H NMR 结合作为一种发现工具，不仅可以用于已知化合物的去复制品鉴定，还可以用于挖掘未开发的化合物库。
