Castro-Falcón Gabriel, Guillén-Matus Dulce G, Da Silva Elany Barbosa, Guo Wentao, Ross Alicia, Serafim Mateus Sá Magalhães, Fernandes Thais Helena Maciel, Tantillo Dean J, O'Donoghue Anthony J, Jensen Paul R
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Skaggs School of Pharmacy and Pharmaceutical Sciences, Center for Discovery and Innovation in Parasitic Diseases, University of California San Diego, La Jolla, California 92093, United States.
bioRxiv. 2024 Oct 30:2024.10.29.620863. doi: 10.1101/2024.10.29.620863.
We report three new ketomemicin pseudopeptides (-) from extracts of the marine actinomycete strain CNY-498. Their constitution and relative configuration were elucidated using NMR, mass spectrometry, and quantum chemical calculations. Using GNPS molecular networking and publicly available LCMS datasets, five additional ketomemicin analogs (-) were identified with ketomemicin production detected broadly across species. The ketomemicin biosynthetic gene cluster () is highly conserved in , occurring in 79 of 118 public genome sequences including eight of the nine named species. Outside homologs were detected in various genera of the phylum Actinomycetota that might encode novel ketomemicin analogs. Ketomemicins - were tested against a panel of eleven proteases, with displaying moderate inhibitory activity. This study describes the first report of ketomemicin production by cultures, the distribution of the corresponding biosynthetic gene cluster, and the protease inhibitory activity of new ketomemicin derivatives.
我们报道了从海洋放线菌菌株CNY - 498提取物中获得的三种新的酮霉素假肽（-）。利用核磁共振、质谱和量子化学计算对它们的结构和相对构型进行了阐明。通过使用全球天然产物社会分子网络（GNPS）和公开可用的液相色谱 - 质谱数据集，又鉴定出了另外五种酮霉素类似物（-），并且在多个物种中广泛检测到了酮霉素的产生。酮霉素生物合成基因簇（）在中高度保守，在118个公共基因组序列中的79个中存在，包括九个命名物种中的八个。在放线菌门的各个属中检测到了外部同源物，这些同源物可能编码新的酮霉素类似物。对酮霉素 - 进行了针对一组十一种蛋白酶的测试，其中显示出中等抑制活性。本研究描述了关于培养物产生酮霉素的首次报道、相应生物合成基因簇的分布以及新酮霉素衍生物的蛋白酶抑制活性。
