通过NMR代谢组学和基因组分析的综合，可以提供增强的结构特性鉴定以及关键生物合成信息，从而实现对新天然产物的有针对性的发现。为此，对海洋源性链霉菌菌株Streptomyces sp. S063（CGMCC 14582）进行了基于NMR的代谢组学分析，通过该分析追踪到了具有异常负1H NMR化学位移值的N-甲基化肽。与此同时，对该菌株进行基因组挖掘发现了一个含有噁唑酸编码基因（lenE和lenF）的未知NRPS基因簇（len）。在综合信息的指导下，从Streptomyces sp. S063中分离得到了两种环肽化合物lenziamide D1（1）和B1（2），其中含有负1H NMR值的噁唑酸。通过广泛的光谱分析结合Marfey法和ECD计算的方法来确定了1和2的结构。此外，我们还提供了Streptomyces sp. S063中lenziamide（1和2）的生物合成详细模型。在细胞毒性评估中，1和2对人类癌细胞HEL，H1975，H1299和耐药性A549-taxol表现出中等生长抑制作用，IC50值为8-24 μM。

The integration of NMR-metabolomic and genomic analyses can provide enhanced identification of structural properties as well as key biosynthetic information, thus achieving the targeted discovery of new natural products. For this purpose, NMR-based metabolomic profiling of the marine-derived Streptomyces sp. S063 (CGMCC 14582) was performed, by which N-methylated peptides possessing unusual negative 1H NMR chemical shift values were tracked. Meanwhile, genome mining of this strain revealed the presence of an unknown NRPS gene cluster (len) with piperazic-acid-encoding genes (lenE and lenF). Under the guidance of the combined information, two cyclic decapeptides, lenziamides D1 (1) and B1 (2), were isolated from Streptomyces sp. S063, which contains piperazic acids with negative 1H NMR values. The structures of 1 and 2 were determined by extensive spectroscopic analysis combined with Marfey's method and ECD calculations. Furthermore, we provided a detailed model of lenziamide (1 and 2) biosynthesis in Streptomyces sp. S063. In the cytotoxicity evaluation, 1 and 2 showed moderate growth inhibition against the human cancer cells HEL, H1975, H1299, and drug-resistant A549-taxol with IC50 values of 8-24 μM.