Unconventional approaches for the induction of microbial natural products

Expansion of the microbial drug discovery pipeline has been impeded by a limited and skewed appreciation of the microbial world and its full chemical capabilities and by an inability to induce silent biosynthetic gene clusters (BGCs). Typically, these silent genes are not expressed under standard laboratory conditions, instead requiring particular interventions to activate them. Genetic, physical, and chemical strategies have been employed to trigger these BGCs, and some have resulted in the induction of novel secondary metabolites. This review encompasses a wide range of literature and emphasizes selected successful induction of microbial secondary metabolites examples through unconventional approaches such as quorum sensing, epigenetic modulation, and ribosome engineering. Whenever applicable, we will also discuss their mechanisms and optimizations to improve the microbial drug discovery process.