Structure-activity relationship of lariatin

套索蛋白的构效关系

• 批准号: 23510282
• 负责人: INOKOSHI Junji
• 金额: $ 3.08万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23510282/
• 关键词: 抗結核活性; 構造活性相関; 感染症; 抗生物質; ペプチド; 蛋白質

Lariatins A and B discovered as an anti-mycobacterial peptides are ribosomally synthesized by Gram positive Rhodococcus jostii. The compounds are unique cyclic peptides, the rigid lasso structure. Production of lariatins in R. jostii is dependent upon a five-gene cluster, larA to larE. We established a simple system of amino acid substitutions of lariatin by R. jostii delta larA, Using this system, mutational scanning of lariatin was carried out. The results showed that three aa residues (G1, R7 and E8) in the circle and three aa residues (W9, V10 and G11) in the threaded segment of the tail are important for lariatin production, and that two aa residues (Y6 and R7) in the circle and four aa residues (7R7, V10, N14 and K17) in the threaded segment of the tail are important for anti-mycobacterial activity. Propeptin biosynthesis gene cluster was identified on the genome of Microbispora rosae. The gene cluster containing the genes corresponding to lar A , B, C and D, but not lar E.

Lariatins A和B是由革兰氏阳性的约氏红球菌（Rhodococcus jostii）核糖体合成的抗分枝杆菌肽。该化合物是独特的环肽，刚性套索结构。在R. jostii依赖于一个五基因簇，larA到larE。我们建立了一个简单的由R.利用该系统对lariatin基因进行了突变扫描。结果表明，三个aa残基（G1、R7和E8）和三个aa残基因此，尾部螺纹段中的两个氨基酸残基（W9、V10和G11）对于拉里菌素生产是重要的，并且环中的两个氨基酸残基（Y6和R7）和尾部螺纹段中的四个氨基酸残基（7R7、V10、N14和K17）对于抗分枝杆菌活性是重要的。在玫瑰小双孢菌基因组上发现了前肽素生物合成基因簇。该基因簇含有与larA、B、C和D对应的基因，但不含larE。

项目成果

抗結核活性を示す放線菌由来投げ縄ペプチド・lariatinの生合成機構の解析とアミノ酸置換変異体の構造活性相関

放线菌套索肽Lariatin抗结核生物合成机制及氨基酸取代突变体构效关系分析

• 发表时间: 2012
• 作者: 猪腰淳嗣 ,供田洋

Analysis of essential amino acids in lasso peptide lariatins for anti-mycobacterial activity by single amino acid substitution

通过单氨基酸取代分析套索肽套索中必需氨基酸的抗分枝杆菌活性

• 发表时间: 2012
• 作者: J. Inokoshi;M. Miyake;Y. Shimizu;H. Tomoda
• 通讯作者: H. Tomoda

Molecular cloning of the gene cluster for lariatin biosynthesis of Rhodococcus jostii K01-B0171

• DOI: 10.1007/s00253-012-3973-8
• 发表时间: 2012-07-01
• 期刊: APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
• 影响因子: 5
• 作者: Inokoshi, Junji;Matsuhama, Maki;Tomoda, Hiroshi
• 通讯作者: Tomoda, Hiroshi