School of Life Sciences, Ludong University, Yantai 264025, China.
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
Fitoterapia. 2023 Jun;167:105503. doi: 10.1016/j.fitote.2023.105503. Epub 2023 Apr 8.
Natural products have been playing an indispensable role in drug discovery. However, it seems that the golden period of discovering new compounds has passed since the first antibiotic-penicillin. With the development of genome sequencing, it has been found that marine fungi contain various biosynthetic gene clusters (BGCs), which are silent under standard laboratory conditions. Therefore, it might be envisioned that once these BGCs are expressed, a large quantity of new secondary metabolites with biological activities could be generated. This paper reviewed several activation techniques implemented from 2020 to 2022, including epigenetics regulation, co-culture, precursor feeding, heterologous expression, and changing fermentation parameters to activate silent BGCs of marine fungi. We also described the diversity and bioactivities of these newly discovered uncommon marine fungi-derived compounds based on the classification of activation techniques, facilitating research groups focusing on natural products to enhance discovering efficiency.
天然产物在药物发现中一直发挥着不可或缺的作用。然而,自从发现第一种抗生素——青霉素以来,似乎新化合物的发现黄金时期已经过去。随着基因组测序的发展,人们发现海洋真菌中含有各种生物合成基因簇(BGCs),在标准实验室条件下这些 BGCs 处于沉默状态。因此,可以想象,一旦这些 BGCs 被表达,就可能产生大量具有生物活性的新型次级代谢产物。本文综述了 2020 年至 2022 年实施的几种激活技术,包括表观遗传学调控、共培养、前体喂养、异源表达以及改变发酵参数以激活海洋真菌中沉默的 BGCs。我们还根据激活技术的分类描述了这些新发现的海洋真菌衍生化合物的多样性和生物活性,为专注于天然产物的研究小组提供便利,以提高发现效率。