Discovery of Antimycin-Type Depsipeptides from a wbl Gene Mutant Strain of Deepsea-Derived Streptomyces somaliensis SCSIO ZH66 and Their Effects on Pro-inflammatory Cytokine Production
Li, HY; Huang, HM; Hou, LK; Ju, JH; Li, WL; liwenli@ouc.edu.cn
2017
发表期刊FRONTIERS IN MICROBIOLOGY
卷号8页码:678-
摘要Deepsea microbes are a rich source of novel bioactive compounds, which have developed unique genetic systems as well as biosynthetic pathways compared with those of terrestrial microbes in order to survive in extreme living environment. However, a large variety of deepsea-microbial secondary metabolic pathways remain "cryptic" under the normal laboratory conditions. Manipulation of global regulators is one of the effective approaches for triggering the production of cryptic secondary metabolites. In this study, by combination of various chromatographic purification process, we obtained somalimycin (1), a new antimycin-type depsipeptide, with an unusual substitution of 3-aminosalicylate instead of conserved 3-formamidosalicylate moiety, along with two known (2 and 3) analogs from the 1 wblA(so) mutant strain of deepsea-derived Streptomyces somaliensis SCSIO ZH66. The structures of 1-3 were elucidated on the basis of extensive spectroscopic analyses including LC-MS and NMR. In the evaluation of potent anti-inflammatory activity, compound 2 exhibited strong inhibitory activity on the IL-5 production in ovalbumin-stimulated splenocytes with IC50 value of 0.57 mu M, while 1 and 3 displayed mild effect (> 10 mu M), which might be attributed to their different side-chain substitutions. Moreover, compounds 1-3 showed very weak cytotoxicity against human umbilical vein endothelial cells with LD50 values of 62.6, 34.6, and 192.9 mu M, respectively, which were far over their IL-5 inhibitory activity. These results indicated that these compounds have good potential for further use in anti-inflammatory drug development.
部门归属[Li, Huayue; Huang, Huiming; Hou, Lukuan; Li, Wenli] Ocean Univ China, Sch Med & Pharm, Minist Educ, Key Lab Marine Drugs, Qingdao, Peoples R China; [Ju, Jianhua] Chinese Acad Sci, South China Sea Inst Oceanol, RNAM Ctr Marine Microbiol, Guangdong Key Lab Marine Mat Med,CAS Key Lab Mari, Guangzhou, Guangdong, Peoples R China; [Li, Wenli] Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao, Peoples R China
关键词Antimycin-type Depsipeptides Deepsea-derived Bacteria Regulatory Gene Anti-inflammatory Il-5 Production
资助项目LMB
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/16265
专题中科院海洋生物资源可持续利用重点实验室
通讯作者liwenli@ouc.edu.cn
推荐引用方式
GB/T 7714
Li, HY,Huang, HM,Hou, LK,et al. Discovery of Antimycin-Type Depsipeptides from a wbl Gene Mutant Strain of Deepsea-Derived Streptomyces somaliensis SCSIO ZH66 and Their Effects on Pro-inflammatory Cytokine Production[J]. FRONTIERS IN MICROBIOLOGY,2017,8:678-.
APA Li, HY,Huang, HM,Hou, LK,Ju, JH,Li, WL,&liwenli@ouc.edu.cn.(2017).Discovery of Antimycin-Type Depsipeptides from a wbl Gene Mutant Strain of Deepsea-Derived Streptomyces somaliensis SCSIO ZH66 and Their Effects on Pro-inflammatory Cytokine Production.FRONTIERS IN MICROBIOLOGY,8,678-.
MLA Li, HY,et al."Discovery of Antimycin-Type Depsipeptides from a wbl Gene Mutant Strain of Deepsea-Derived Streptomyces somaliensis SCSIO ZH66 and Their Effects on Pro-inflammatory Cytokine Production".FRONTIERS IN MICROBIOLOGY 8(2017):678-.
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