两性霉素B合成基因簇及其组合生物学进展

Researches on the gene clusters of amphotericin B and its combinatorial biology

两性霉素B(AmB)作为第一个用于深部真菌感染的药物,自上市以来已使用超过半个世纪,目前仍是临床治疗中不可缺少的药物。随着近年来AmB衍生物药物的发展,以及其生产菌株结节链霉菌(Streptomyces nodosus)全基因组和AmB体内合成代谢途径的解析,运用基因工程和代谢工程的方法对AmB组合生物合成的研究逐渐增多。由于AmB在当今临床治疗上的地位仍极其重要,因此促进AmB产业的发展具有显著的经济及社会效益。本文对AmB进行了概述,并对其合成基因簇相关基因及其当前组合生物合成的研究现况进行了总结与探讨。

Amphotericin B, as the first drug against deep fungal infection which has been used for more than fifty years, is still an indispensable antibiotic in clinical treatment. In recent years, with the development of Arab derivatives, the analysis of genome of the Streptomyces nodosus and the metabolic pathways of AraB, more and more strategies involving genetic engineering and metabolic engineering were used to study the combinatorial biosynthesis of AraB. It＇s obviously AmB paly an important role in clinical treatment, for this reason developing the production of AraB has significant economic and social benefits. Herein, a brief summary of AraB, the organization of the AmBiosynthetie gene cluster and its current combinatorial biosynthesis is reviewed.