Thissera Bathini, Soldatou Sylvia, Belbahri Lassaad, Ebel Rainer, Jaspars Marcel, Rateb Mostafa E
School of Computing, Engineering & Physical Sciences, University of the West of Scotland, High Street, Paisley PA1 2BE, Scotland, UK.
Department of Chemistry, Marine Biodiscovery Centre, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK.
J Appl Microbiol. 2025 Jan 6;136(1). doi: 10.1093/jambio/lxaf014.
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.
对微生物世界及其完整化学能力的认识有限且存在偏差，以及无法诱导沉默生物合成基因簇（BGCs），阻碍了微生物药物发现管道的扩展。通常，这些沉默基因在标准实验室条件下不表达，而是需要特定干预来激活它们。已采用遗传、物理和化学策略来触发这些BGCs，其中一些策略已导致新型次级代谢产物的诱导。本综述涵盖了广泛的文献，并强调了通过群体感应、表观遗传调控和核糖体工程等非常规方法成功诱导微生物次级代谢产物的选定实例。只要适用，我们还将讨论它们的机制和优化方法，以改进微生物药物发现过程。
