中国科学院上海有机化学研究所机构知识库
Advanced  
SIOC OpenIR  > 生命有机化学国家重点实验室  > 期刊论文
学科主题: 生命有机化学
题名: Operon for Biosynthesis of Lipstatin, the Beta-Lactone Inhibitor of Human Pancreatic Lipase
其他题名: 生物合成人胰脂肪酶抑制剂β-内酯lipstatin的操纵子
作者: BAI TINGLI1; Zhang DZ(张道忠)1; LIN SHUANGJUN1; LONG QINGSHAN1; WANG YEMIN1; OU HONGYU1; KANG QIANJIN1; DENG ZIXIN1; Liu W(刘文)1; TAO MEIFENG1
通讯作者: TAO MEIFENG
刊名: Appl. Environ. Microbiol.
发表日期: 2014
DOI: 10.1128/AEM.01765-14
卷: 80, 期:24, 页:7473-7483
收录类别: SCI
英文摘要: Lipstatin, isolated from Streptomyces toxytricini as a potent and selective inhibitor of human pancreatic lipase, is a precursor for tetrahydrolipstatin (also known as orlistat, Xenical, and Alli), the only FDA-approved antiobesity medication for long-term use. Lipstatin features a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-beta-lactone structure with an N-formyl-L-leucine group attached as an ester to the 5-hydroxy group. It has been suggested that the alpha-branched 3,5-dihydroxy fatty acid beta-lactone moiety of lipstatin in S. toxytricini is derived from Claisen condensation between two fatty acid substrates, which are derived from incomplete oxidative degradation of linoleic acid based on feeding experiments. In this study, we identified a six-gene operon (lst) that was essential for the biosynthesis of lipstatin by large-deletion, complementation, and single-gene knockout experiments. lstA, lstB, and lstC, which encode two beta-ketoacyl-acyl carrier protein synthase III homologues and an acyl coenzyme A (acyl-CoA) synthetase homologue, were indicated to be responsible for the generation of the alpha-branched 3,5-dihydroxy fatty acid backbone. Subsequently, the nonribosomal peptide synthetase (NRPS) gene lstE and the putative formyltransferase gene lstF were involved in decoration of the alpha-branched 3,5-dihydroxy fatty acid chain with an N-formylated leucine residue. Finally, the 3 beta-hydroxysteroid dehydrogenase-homologous gene lstD might be responsible for the reduction of the beta-keto group of the biosynthetic intermediate, thereby facilitating the formation of the unique beta-lactone ring.
语种: 英语
相关网址: 查看原文
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/38963
Appears in Collections:生命有机化学国家重点实验室_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
2014558.pdf(1240KB)期刊论文作者接受稿开放获取View Download

作者单位: 1.上海交通大学
2.中科院上海有机化学研究所
3.华中农业大学

Recommended Citation:
BAI TINGLI,Zhang DZ,LIN SHUANGJUN,et al. Operon for Biosynthesis of Lipstatin, the Beta-Lactone Inhibitor of Human Pancreatic Lipase[J]. Appl. Environ. Microbiol.,2014,80(24):7473-7483.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[BAI TINGLI]'s Articles
[张道忠]'s Articles
[LIN SHUANGJUN]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[BAI TINGLI]‘s Articles
[张道忠]‘s Articles
[LIN SHUANGJUN]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: 2014558.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Powered by CSpace