State Key Laboratory of Microbial Metabolism and School of Life Science & Biotechnology, State Key Laboratory of Ocean Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Mar Drugs. 2013 Oct 22;11(10):4035-49. doi: 10.3390/md11104035.
The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.
从红树林来源的链霉菌菌株 Streptomyces xiamenensis 318 中培养得到的苯并吡喃化合物具有多种生物学效应，包括抗纤维化和抗增生性瘢痕特性。为了增加现有苯并吡喃结构的多样性，通过生物合成，筛选该菌株以获得自发的利福平抗性（Rif），并将赋予链霉素抗性（Str）的突变 rpsL 基因导入源自深海沉积物的 S. xiamenensis 菌株 M1-94P。从 M1-94P 的 Str-Rif 双突变体（M6）的粗提物中分离得到两种新的苯并吡喃衍生物，命名为 xiamenmycin C（1）和 D（2）。通过分析广泛的光谱数据确定了 1 和 2 的结构。化合物 1 和 2 均抑制人肺成纤维细胞（WI26）的增殖，并且 1 显示出比 xiamenmycin 更好的抗纤维化活性。本研究从核糖体工程构建的 S. xiamenensis 突变株 M6 中分离出新型生物活性化合物，这可能是发现新型抗纤维化化合物的有用方法。
