Pan Rui, Bai Xuelian, Chen Jianwei, Zhang Huawei, Wang Hong
School of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.
College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
Front Microbiol. 2019 Feb 26;10:294. doi: 10.3389/fmicb.2019.00294. eCollection 2019.
Microbial secondary metabolites (MSMs) have played and continue to play a highly significant role in the drug discovery and development process. Genetically, MSM chemical structures are biologically synthesized by microbial gene clusters. Recently, however, the speed of new bioactive MSM discovery has been slowing down due to consistent employment of conventional cultivation and isolation procedure. In order to alleviate this challenge, a number of new approaches have been developed. The strategy of one strain many compounds (OSMAC) has been shown as a simple and powerful tool that can activate many silent biogenetic gene clusters in microorganisms to make more natural products. This review highlights important and successful examples using OSMAC approaches, which covers changing medium composition and cultivation status, co-cultivation with other strain(s), adding enzyme inhibitor(s) and MSM biosynthetic precursor(s). Available evidences had shown that variation of cultivation condition is the most effective way to produce more MSMs and facilitate the discovery of new therapeutic agents.
微生物次级代谢产物（MSMs）在药物发现和开发过程中一直发挥着极其重要的作用，并且仍将继续发挥重要作用。从基因角度来看，MSM的化学结构是由微生物基因簇进行生物合成的。然而，近来由于传统培养和分离方法的持续使用，新型生物活性MSM的发现速度一直在放缓。为了应对这一挑战，人们开发了许多新方法。“一株多化合物”（OSMAC）策略已被证明是一种简单而强大的工具，它可以激活微生物中许多沉默的生物遗传基因簇，从而产生更多天然产物。本综述重点介绍了使用OSMAC方法的重要且成功的实例，这些实例包括改变培养基成分和培养条件、与其他菌株共培养、添加酶抑制剂和MSM生物合成前体。现有证据表明，改变培养条件是产生更多MSM并促进新型治疗药物发现的最有效方法。
