Structure-activity relationship of lariatin

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。

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.