Construction of a meroterpenoid-like compound collection by precursor-assisted biosynthesis
Construction of a meroterpenoid-like compound collection by precursor-assisted biosynthesis
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通过前体辅助生物合成构建类萜化合物集合
DOI：
10.1039/d0ob01235a
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发表时间：
2020
影响因子：
3.2
通讯作者：
Yang Yan-Long
中科院分区：
文献类型：
--
作者：
Ren Panlong;Miao Xinyu;Tang Ting;Wu Yueting;Wang Jing;Zeng Ying;Li Yun;Gao Kun;Yang Yan-Long
天然产物（NPs）及其衍生物由于其复杂性和多样性在药物发现中起着关键作用。快速生成np样化合物的策略为获得生物活性化合物提供了独特的机会。在这里，我们提出了一种新的方法，前体辅助生物合成（PAB），通过人工补充常见前体和对缺乏前体的真菌进行不同的后修饰来创造np样化合物。应用该方法构建了包含43个具有不同分子支架的类甲萜类化合物集合。广泛的生物活性筛选发现了新的STING（干扰素基因刺激因子）抑制剂，细胞毒性和抗真菌化合物。这一结果表明，PAB是一种有效的方法，以产生化合物收集为目的的药物发现。
Natural products (NPs) and their derivatives play a pivotal role in drug discovery due to their complexity and diversity. The strategies to rapidly generate NP-like compounds offer unique opportunities to access bioactive compounds. Here we present a new approach, precursor-assisted biosynthesis (PAB), for the creation of NP-like compounds by combination of artificial supplementation of common precursors and divergent post-modifications of precursor-deficient fungi. This method was applied to construct a meroterpenoid-like compound collection containing 43 compounds with diverse molecular scaffolds. Extensive bioactive screening of the collection revealed novel STING (stimulator of interferon genes) inhibitors, cytotoxic and antifungal compounds. This result indicates that PAB is an effective methodology for producing compound collections for the purpose of drug discovery.