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首页> 外文期刊>The Journal of Antibiotics: An International Journal >New natural products isolated from Metarhizium robertsii ARSEF 23 by chemical screening and identification of the gene cluster through engineered biosynthesis in Aspergillus nidulans A1145
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New natural products isolated from Metarhizium robertsii ARSEF 23 by chemical screening and identification of the gene cluster through engineered biosynthesis in Aspergillus nidulans A1145

机译：通过在Aspergillus Nidulans A1145中通过工程化生物合成的化学筛选和鉴定基因群中的新自然产品。

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摘要

To rapidly identify novel natural products and their associated biosynthetic genes from underutilized and genetically difficult-to-manipulate microbes, we developed a method that uses (1) chemical screening to isolate novel microbial secondary metabolites, (2) bioinformatic analyses to identify a potential biosynthetic gene cluster and (3) heterologous expression of the genes in a convenient host to confirm the identity of the gene cluster and the proposed biosynthetic mechanism. The chemical screen was achieved by searching known natural product databases with data from liquid chromatographic and high-resolution mass spectrometric analyses collected on the extract from a target microbe culture. Using this method, we were able to isolate two new meroterpenes, subglutinols C (1) and D (2), from an entomopathogenic filamentous fungus Metarhizium robertsii ARSEF 23. Bioinformatics analysis of the genome allowed us to identify a gene cluster likely to be responsible for the formation of subglutinols. Heterologous expression of three genes from the gene cluster encoding a polyketide synthase, a prenyltransferase and a geranylgeranyl pyrophosphate synthase in Aspergillus nidulans A1145 afforded an alpha-pyrone-fused uncyclized diterpene, the expected intermediate of the subglutinol biosynthesis, thereby confirming the gene cluster to be responsible for the subglutinol biosynthesis. These results indicate the usefulness of our methodology in isolating new natural products and identifying their associated biosynthetic gene cluster from microbes that are not amenable to genetic manipulation. Our method should facilitate the natural product discovery efforts by expediting the identification of new secondary metabolites and their associated biosynthetic genes from a wider source of microbes.
机译：为了快速识别新的天然产物和其相关的生物合成基因的未充分利用和遗传困难的微生物，我们开发了一种使用（1）化学筛选来分离新的微生物次级代谢物，（2）生物信息分析以确定潜在的生物合成的方法基因簇和（3）基因的异源表达在方便的宿主中，以确认基因簇的身份和所提出的生物合成机制。通过从液相色谱和高分辨率从靶微生物培养物上收集的液体色谱和高分辨率质谱分析来搜索已知的天然产品数据库来实现化学筛网。使用这种方法，我们能够分离出两种新的梅特萜烯，sub凝集素c（1）和d（2），来自昆虫疗法丝状真菌细胞群罗伯苏里Arsef 23.基因组的生物信息学分析使我们鉴定可能是负责的基因集群形成subglutinols。来自编码聚酮合成酶的基因簇的三种基因的异源表达，胰腺癌A1145中戊酮和焦磷酸焦磷酸酯合成酶，得到α-吡喃酮稠合的未循环二萜，预期的子凝集蛋白生物合成中间体，从而证实基因聚类负责subglutinol生物合成。这些结果表明了我们在分离新的天然产物中并鉴定它们与遗传操作不适合的微生物相关的生物合成基因簇的有用性。我们的方法应通过加速来自更广泛的微生物来源的新的次级代谢产物及其相关的生物合成基因来促进自然产品发现努力。

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