Pandey Ankesh, Israr Juveriya, Pandey Janmejay, Misra Sankalp
Department of Biotechnology, Meerut Institute of Engineering and Technology, Meerut, 250005, Uttar Pradesh, India.
Department of Biotechnology, Era University, Lucknow, Uttar Pradesh, India.
Curr Microbiol. 2025 Apr 22;82(6):258. doi: 10.1007/s00284-025-04237-7.
Bioactive Natural Products (BNPs) are in high demand due to their disease-preventive capabilities and resistance to pathogens. However, our understanding of BNP-producing microbes is limited, because many microbial populations remain uncultivated. Various approaches have been employed to explore the potential of these hidden microbes for new bioactive therapeutic compounds. Nevertheless, the possibility of discovering BNPs from microbial communities is largely cryptic due to their unculturable nature and the absence of triggers to activate the dormant Biosynthetic Gene Clusters (BGCs). Metagenome sequencing, followed by mining and characterization, is an effective approach for discovering new therapeutic BNPs. The inactive state of BGCs can be activated through the combinatorial interaction of different microbial communities within a common niche, overcoming programmable co-evolutionary stress and producing new BNPs. The present review discusses and explores the potential of hidden, uncultivated microbes for discovering novel Bioactive Natural Products (BNPs). Moreover, it provides insights into optimizing microbial production systems and fostering sustainable drug discovery and development practices by integrating multidisciplinary strategies. This review also emphasizes the critical role of microbial sources in the ongoing search for new bioactive products that can meet the demands of modern healthcare and environmental sustainability.
生物活性天然产物（BNPs）因其疾病预防能力和对病原体的抗性而需求旺盛。然而，我们对产生BNP的微生物的了解有限，因为许多微生物种群仍未得到培养。人们已采用各种方法来探索这些隐藏微生物产生新型生物活性治疗化合物的潜力。尽管如此，由于微生物群落不可培养的特性以及缺乏激活休眠生物合成基因簇（BGCs）的触发因素，从微生物群落中发现BNPs的可能性在很大程度上仍是未知的。宏基因组测序，随后进行挖掘和表征，是发现新型治疗性BNPs的有效方法。BGCs的非活性状态可以通过共同生态位内不同微生物群落的组合相互作用来激活，克服可编程的共同进化压力并产生新的BNPs。本综述讨论并探索了隐藏的、未培养微生物在发现新型生物活性天然产物（BNPs）方面的潜力。此外，它还通过整合多学科策略，为优化微生物生产系统以及促进可持续药物发现和开发实践提供了见解。本综述还强调了微生物来源在持续寻找能够满足现代医疗保健和环境可持续性需求的新型生物活性产品中的关键作用。
