Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun South Street, Beijing, 100081, People's Republic of China.
The National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, 12 Zhongguancun South Street, Beijing 100081, People's Republic of China.
J Nat Prod. 2023 May 26;86(5):1240-1250. doi: 10.1021/acs.jnatprod.2c01168. Epub 2023 May 5.
Mass spectrometry-based dereplication and prioritization led to the discovery of four multi--methylated cyclodecapeptides, auyuittuqamides E-H (-), from a soil-derived sp. The planar structures of these compounds were elucidated based on analysis of HRESIMS and NMR data. Absolute configurations of the chiral amino acid residues were assigned by a combination of the advanced Marfey's method, chiral-phase LC-MS analysis, and -based configuration analysis, revealing that - contain both d- and l-isomers of -methylleucine (MeLeu). Differentiation of d- and l-MeLeu in the sequence was achieved by advanced Marfey's analysis of the diagnostic peptide fragments generated from partial hydrolysis of . Bioinformatic analysis identified a putative biosynthetic gene cluster () for auyuittuqamides E-H, and a plausible biosynthetic pathway was proposed. These newly identified fungal cyclodecapeptides (-) displayed growth inhibitory activity against vancomycin-resistant with MIC values of 8 μg/mL.
基于质谱的去冗余和优先级排序，从土壤中分离出一种真菌 sp.，发现了四种多甲基化的环十肽，即 auyuittuqamides E-H（-）。这些化合物的平面结构是根据 HRESIMS 和 NMR 数据分析得出的。通过先进的 Marfey 法、手性相 LC-MS 分析和基于计算的构型分析相结合，确定了手性氨基酸残基的绝对构型，表明 - 含有 - 甲基亮氨酸（MeLeu）的 d-和 l-异构体。通过对部分水解产生的诊断肽片段进行先进的 Marfey 分析，在序列中区分了 d-和 l-MeLeu。生物信息学分析鉴定了 auyuittuqamides E-H 的一个假定生物合成基因簇（），并提出了一个可能的生物合成途径。这些新鉴定的真菌环十肽（-）对万古霉素耐药的具有生长抑制活性，MIC 值为 8 μg/mL。
