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4-Hydroxy Pyridones from Heterologous Expression and Cultivation of the Native Host
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-10-23 , DOI: 10.1021/acs.jnatprod.0c00675 Wei-Yang Zhang 1 , Yue Zhong 1 , Yang Yu 2 , Dan-Feng Shi 2 , Hui-Yun Huang 2 , Xiao-Long Tang 1 , Yong-Heng Wang 2 , Guo-Dong Chen 2 , Hui-Ping Zhang 3 , Chen-Li Liu 1 , Dan Hu 2 , Hao Gao 2 , Xin-Sheng Yao 2
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-10-23 , DOI: 10.1021/acs.jnatprod.0c00675 Wei-Yang Zhang 1 , Yue Zhong 1 , Yang Yu 2 , Dan-Feng Shi 2 , Hui-Yun Huang 2 , Xiao-Long Tang 1 , Yong-Heng Wang 2 , Guo-Dong Chen 2 , Hui-Ping Zhang 3 , Chen-Li Liu 1 , Dan Hu 2 , Hao Gao 2 , Xin-Sheng Yao 2
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4-Hydroxy pyridones are a class of fungi-derived polyketide–nonribosomal peptide products featuring a core of 4-hydroxy-2-pyridone which have a wide range of biological activities. Genome mining of in-house strains using polyketide synthase–nonribosomal peptide synthase as a query identified an endophyte Tolypocladium sp. 49Y, which possesses a potential 4-hydroxy pyridone biosynthetic gene cluster. Heterologous expression in Aspergillus oryzae NSAR1 revealed that this gene cluster is functional and able to produce a rare type of 4-hydroxy pyridones called tolypyridones (compounds 3 and 4). Tolypocladium sp. 49Y was grown in a variety of media which led to the isolation of six 4-hydroxy pyridones (5–10) and one pyrrolidone (11) from a rice culture, and compounds 3 and 9 showed antifungal activity. These latter compounds are different from those obtained by heterologous expression. This study shows that both heterologous expression and cultivation of the native host are complementary approaches to discover new natural products.
中文翻译：
来自本地宿主异源表达和培养的 4-羟基吡啶酮
4-羟基吡啶酮是一类以4-羟基-2-吡啶酮为核心的真菌衍生聚酮化合物-非核糖体肽产品，具有广泛的生物活性。使用聚酮化合物合酶-非核糖体肽合酶作为查询的内部菌株的基因组挖掘确定了一种内生菌Tolypocladium sp。49Y，具有潜在的 4-羟基吡啶酮生物合成基因簇。Aspergillus oryzae NSAR1 中的异源表达表明，该基因簇具有功能性，能够产生一种罕见的 4-羟基吡啶酮，称为甲苯吡啶酮（化合物3和4）。Tolypocladium sp. 49Y 在多种培养基中生长，导致分离出 6 个 4-羟基吡啶酮（5 – 10 ) 和一种来自水稻培养物的吡咯烷酮 ( 11 ) 和化合物3和9显示出抗真菌活性。这些后面的化合物不同于通过异源表达获得的那些。这项研究表明，本地宿主的异源表达和培养都是发现新天然产物的互补方法。
更新日期：2020-11-25
中文翻译：
来自本地宿主异源表达和培养的 4-羟基吡啶酮
4-羟基吡啶酮是一类以4-羟基-2-吡啶酮为核心的真菌衍生聚酮化合物-非核糖体肽产品，具有广泛的生物活性。使用聚酮化合物合酶-非核糖体肽合酶作为查询的内部菌株的基因组挖掘确定了一种内生菌Tolypocladium sp。49Y，具有潜在的 4-羟基吡啶酮生物合成基因簇。Aspergillus oryzae NSAR1 中的异源表达表明，该基因簇具有功能性，能够产生一种罕见的 4-羟基吡啶酮，称为甲苯吡啶酮（化合物3和4）。Tolypocladium sp. 49Y 在多种培养基中生长，导致分离出 6 个 4-羟基吡啶酮（5 – 10 ) 和一种来自水稻培养物的吡咯烷酮 ( 11 ) 和化合物3和9显示出抗真菌活性。这些后面的化合物不同于通过异源表达获得的那些。这项研究表明，本地宿主的异源表达和培养都是发现新天然产物的互补方法。
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