Structure-activity relationship of lariatin

拉里菌素A和B是由革兰氏阳性约氏红球菌核糖体合成的一种抗分枝杆菌多肽。这些化合物是独特的环肽，刚性套索结构。在r.jostii中，lariatins的生产依赖于一个5个基因簇，即lara到lare。我们建立了一个简单的约氏乳杆菌拉丁氨基酸取代体系，并利用该体系对拉丁进行了突变扫描。结果表明，环状结构中的3个氨基酸残基(G1、R7和E8)和尾部螺纹段的3个氨基酸残基(W9、V10和G11)对马兜铃素的产生起重要作用；环状结构中的2个氨基酸残基(Y6和R7)和尾部螺纹段的4个氨基酸残基(7R7、V10、N14和K17)对抗分枝杆菌活性起重要作用。在玫瑰小双孢菌基因组上发现了ProPeptin生物合成基因簇。基因簇包含与大A、B、C和D对应的基因，但不包含大E。

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.