Wu Sifan, Huang Tingting, Xie Dan, Wo Jing, Wang Xiaozheng, Deng Zixin, Lin Shuangjun
State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
J Antibiot (Tokyo). 2017 Jan;70(1):90-95. doi: 10.1038/ja.2016.60. Epub 2016 Jun 22.
Xantholipin is a polycyclic xanthone antibiotic that exhibits potent cytotoxic and antibacterial activity. In this study, a new xanthone-type antibiotic, xantholipin B (1), was isolated for the first time along with its known derivative, xantholipin (2), from strain WJN-1, an aminotransferase inactivation mutant of the streptonigrin-producer Streptomyces flocculus CGMCC 4.1223. The structure of 1 was established based on spectroscopic analysis and supports the previously proposed biosynthetic pathway as a key intermediate of 2. Moreover, 1 showed 3- to 10-fold greater cytotoxicity than 2 against a select panel of human cancer cell lines. In addition, 1 demonstrated powerful antimicrobial activity against both Gram-positive bacteria and fungi. Importantly, both 1 and 2 inhibited the methicillin-resistant strain Staphylococcus aureus Mu50, with the MIC value of 0.025 μg ml. The new structural features of 1 enrich the structural diversity of xantholipin family compounds and shed new light on the structure-activity relationship of 1 as a promising antitumor drug candidate.
黄脂素是一种多环呫吨酮抗生素，具有强大的细胞毒性和抗菌活性。在本研究中，首次从链黑菌素产生菌弗氏链霉菌CGMCC 4.1223的转氨酶失活突变体菌株WJN-1中分离出一种新的呫吨酮型抗生素黄脂素B（1）及其已知衍生物黄脂素（2）。1的结构通过光谱分析确定，并支持了先前提出的作为2的关键中间体的生物合成途径。此外，在一组选定的人类癌细胞系中，1的细胞毒性比2大3至10倍。此外，1对革兰氏阳性菌和真菌均表现出强大的抗菌活性。重要的是，1和2均能抑制耐甲氧西林金黄色葡萄球菌Mu50，其MIC值为0.025μg/ml。1的新结构特征丰富了黄脂素家族化合物的结构多样性，并为1作为一种有前景的抗肿瘤药物候选物的构效关系提供了新的线索。
