Sodhi Palakjot Kour, Kour Tanveer, Kaur Gursharan, Gahlaut Vijay, Rath Santosh Kumar, Dwibedi Vagish, Joshi Mahavir
University Institute of Biotechnology, Chandigarh University, Mohali, 140413 Punjab India.
University Center of Research and Development, Chandigarh University, Mohali, 140413 Punjab India.
3 Biotech. 2025 Jun;15(6):156. doi: 10.1007/s13205-025-04328-z. Epub 2025 May 7.
Over the past few decades, microbial-derived bioactive compounds have been tested for antiviral, antimicrobial, and anticancer properties. In addition, fungal-derived bioactive secondary metabolites (SMs) are increasingly being suggested as suitable alternative sources of potent bioactive compounds. The development of suitable, precise in vitro and in vivo screening techniques may contribute to identifying the biochemical and physiological effects of compounds. This advancement in bioassay evaluation techniques helps identify potential bioactive microbes rapidly. The main obstacles, however, have been the production of insufficient amounts of chemicals, endophytes' attenuation or loss of ability to produce the molecule of interest when grown in cultures, and fungal endophytes' failure to exhibit their full biosynthetic potential in lab conditions. These have led to the use of small chemical elicitors that activate the silent biosynthetic gene clusters (BGCs) in fungi, causing epigenetic alterations that increase the amount of desired metabolites or trigger the synthesis of hitherto unknown compounds. The silent BGCs were activated to maximize production of bioactive secondary metabolites, thereby increasing the yield of desired compounds or triggering the synthesis of novel metabolites. Other strategies include gene knocking, inducing mutations, heterologous expression, one strain-many compounds (OSMAC), epigenetic modifications, etc. This review is focused on the mechanism of plant-microbe interaction in enhancing the biosynthesis of fungal metabolites along with the BGCs for the biosynthesis of the bioactive fungal metabolites. Furthermore, we also discuss the genomic mining approaches for BGCs, the role of ribosomal engineering, precursor feeding, and various elicitors to explore the structural diversity of novel bioactive compounds.
在过去几十年中，人们对微生物衍生的生物活性化合物进行了抗病毒、抗菌和抗癌特性测试。此外，越来越多的人认为真菌衍生的生物活性次生代谢产物（SMs）是强效生物活性化合物的合适替代来源。开发合适、精确的体外和体内筛选技术可能有助于确定化合物的生化和生理效应。生物测定评估技术的这一进展有助于快速识别潜在的生物活性微生物。然而，主要障碍包括化学品产量不足、内生菌在培养条件下生长时产生目标分子的能力减弱或丧失，以及真菌内生菌在实验室条件下无法充分发挥其生物合成潜力。这些问题导致人们使用小型化学诱导剂来激活真菌中沉默的生物合成基因簇（BGCs），引起表观遗传改变，从而增加所需代谢产物的量或触发迄今未知化合物的合成。激活沉默的BGCs以最大限度地生产生物活性次生代谢产物，从而提高所需化合物的产量或触发新代谢产物的合成。其他策略包括基因敲除、诱导突变、异源表达、一菌多化合物（OSMAC）、表观遗传修饰等。本综述重点关注植物-微生物相互作用增强真菌代谢产物生物合成的机制以及生物活性真菌代谢产物生物合成的BGCs。此外，我们还讨论了BGCs的基因组挖掘方法、核糖体工程的作用、前体饲喂以及各种诱导剂，以探索新型生物活性化合物的结构多样性。
