OSMAC Strategy: A promising way to explore microbial cyclic peptides

Microbial secondary metabolites are pivotal for the development of novel drugs. However, conventional culture techniques, have left a vast array of unexpressed biosynthetic gene clusters (BGCs) in microorganisms, hindering the discovery of metabolites with distinct structural features and diverse biological functions. To address this limitation, several innovative strategies have been emerged. The “One Strain Many Compounds” (OSMAC) strategy, which involves altering microbial culture conditions, has proven to be particularly effective in mining numerous novel secondary metabolites for the past few years. Among these, microbial cyclic peptides stand out. These peptides often comprise rare amino acids, unique chemical structures, and remarkable biological function. With the advancement of the OSMAC strategy, a plethora of new cyclic peptides have been identified from diverse microbial genera. This work reviews the progress in mining novel compounds using the OSMAC strategy and the applications of this strategy in discovering 284 microbial cyclic peptides from 63 endophytic strains, aiming to offer insights for the further explorations into novel active cyclic peptides. [Display omitted] •Mining microbial cyclic peptides through OSMAC strategy.•The sources, structures and bioactivities of cyclic peptides produced by the OSMAC strategy.•Rare amino acids of microbial cyclic peptides.•Features and applications of the OSMAC strategy.•Combining OSMAC strategy with other pathway-specific strategies.