Structure-activity relationship of lariatin

革兰氏阳性约氏红球菌核糖体合成了抗分枝杆菌肽Lariatins A和B。该化合物是独特的环状肽，具有刚性套索结构。黄毛霉的抗虫素的产生依赖于一个5个基因簇，从larA到larE。本研究建立了一个简单的柔氏夜蛾δ larA氨基酸替代体系，并利用该体系对其进行了突变扫描。结果表明，圆上的3个aa残基（G1、R7和E8）和尾螺纹段的3个aa残基（W9、V10和G11）对幼虫的产生有重要影响，圆上的2个aa残基（Y6和R7）和尾螺纹段的4个aa残基（7R7、V10、N14和K17）对抗分枝杆菌活性有重要影响。在玫瑰微双孢菌基因组上鉴定了促肽生物合成基因簇。包含与大A、B、C和D对应的基因，但不包含大E的基因簇。

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.