达托霉素生物合成研究进展

Advances in daptomycin biosynthesis

摘要:

达托霉素是由玫瑰孢链霉菌(Streptomyces roseosporus)生产的一种环脂肽类抗生素, 具有强大的抗革兰氏阳性致病细菌的作用, 是继“抗生素最后一道防线”万古霉素后的新型抗生素。本文主要对达托霉素的结构、作用机制、合成基因簇及合成机制等当前的研究成果进行综述, 并且总结了利用组合生物学对达托霉素进行结构改造的策略, 以此来研究结构与活性之间的关系, 并寻找更广谱高效的抗生素。最后, 总结了提高达托霉素产量的策略, 为工业上降低达托霉素生产成本提供理论参考。

Abstract:

Daptomycin, produced by Streptomyces roseosporus, is a novel cyclic lipopeptide antibiotic against Gram-positive pathogenic bacteria. It is regarded as a potent antibiotic following vancomycin, the last defense line of antibiotics. This review summarizes the research advances of daptomycin in recent years, mainly including structure, action mechanism, biosynthesis and genes involved in biosynthesis of daptomycin. The strategies of combinatorial biosynthesis are also reviewed to study the relationship between structure and the anti-microbial activity to find potent daptomycin derivatives with a wider spectrum and higher anti-microbial activities. Finally, some strategies to improve daptomycin yields are also introduced, which will be the basis to reduce the daptomycin cost in industrial production.