Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI C1A 4P3, Canada.
Nautilus Biosciences, Croda Canada, Charlottetown, PEI C1A 4P3, Canada.
J Nat Prod. 2024 Jul 26;87(7):1682-1693. doi: 10.1021/acs.jnatprod.3c01234. Epub 2024 Jun 28.
The marine tunicate-derived RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based molecular networking analysis enhanced with nonparametric statistics highlighted the upregulation of a molecular cluster (Kruskal-Wallis = 1.6 e for ) in which no MS/MS features had library matches. Targeted isolation of these features resulted in the discovery of nine new acylated lipopeptides, albubactins A-H (-) each containing a unique glutamine tripeptide and a -terminal ethyl ester moiety. Three related albubactin acids A-C (-) lacking the ethyl ester were also identified. NMR spectroscopy and UPLC-HR-ESI-MS/MS demonstrated that the albubactins were obtained as mixtures that shared a common / and differed only in their acylated terminal groups. Due to the complex spectroscopic elucidation with many overlapping shifts, a total synthesis of albubactin A () was completed and used to determine the absolute configuration of the new albubactins.
为了诱导沉默天然产物的产生，从海洋被囊动物中提取的 RKJM0023 在鼠李糖脂混合物的存在下进行培养。基于 MS/MS 的分子网络分析，并辅以非参数统计，突出了一个分子簇（Kruskal-Wallis = 1.6e）的上调，其中没有 MS/MS 特征与库匹配。对这些特征的靶向分离导致发现了 9 种新的酰化脂肽，即 albubactin A-H (-)，它们各自含有独特的谷氨酰胺三肽和 -末端乙基酯部分。还鉴定了三种缺少乙基酯的相关 albubactin 酸 A-C (-)。NMR 光谱和 UPLC-HR-ESI-MS/MS 表明，albubactins 是作为混合物获得的，它们共享一个共同的 /，并且仅在酰化末端基团上有所不同。由于具有许多重叠位移的复杂光谱阐明，完成了 albubactin A ()的全合成，并用于确定新的 albubactins 的绝对构型。
