Abstract
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.
Highlights
Microbial secondary metabolites (MSMs) have been recognized as the primary source of new compounds for drug discovery and development (Gunatilaka, 2006; Rateb et al, 2011b; Deng et al, 2013)
By mining microbial genome and targeting biosynthetic gene clusters of MSM, researchers can exploit the potential of microbes in a more objective way, such as knocking down, introduction or heterologous expression of microbial genes, regulation of promoters, induction of mutations, or changing cultivation conditions to stimulate MSM genes expression (Schneider et al, 2008)
On basis of extensive literature search, important and successful examples using one strain many compounds (OSMAC) strategy are summarized in this review, which consists of variation of medium, changing cultivation condition, cocultivation with other strain(s), adding epigenetic modifier(s) or biosynthetic precursor(s)
Summary
Microbial secondary metabolites (MSMs) have been recognized as the primary source of new compounds for drug discovery and development (Gunatilaka, 2006; Rateb et al, 2011b; Deng et al, 2013). Traditional chemical investigation of microorganism mainly focuses on extraction and isolation of structurally and highly active compounds from fermentation broth and mycelium. These processes are becoming inefficient due to high rate of the re-discovery of known MSMs. It is commonly believed that a large portion of microbial gene clusters are silenced under standard fermentation conditions (Scherlach and Hertweck, 2009; Wasil et al, 2013). On basis of extensive literature search, important and successful examples using OSMAC strategy are summarized in this review, which consists of variation of medium, changing cultivation condition, cocultivation with other strain(s), adding epigenetic modifier(s) or biosynthetic precursor(s). Inhibitory effect on biofilm formation of Candida albicans with an IC50 value of 1.4 μM (Wang Q.X. et al, 2012)
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