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Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-03-15 00:00:00 , DOI: 10.1021/acschembio.7b00003
Vito Valiante , Derek J. Mattern 1 , Anja Schüffler 2, 3 , Fabian Horn , Grit Walther , Kirstin Scherlach , Lutz Petzke 4 , Joachim Dickhaut 4 , Reinhard Guthke , Christian Hertweck 1 , Markus Nett , Eckhard Thines 2, 3 , Axel A. Brakhage 1
Affiliation  

Filamentous fungi produce a wide range of natural products that are commonly used in various industrial contexts (e.g., pharmaceuticals and insecticides). Meroterpenoids are natural products of interest because of their various biological activities. Among the meroterpenoids, there is a group of insecticidal compounds known as the austinoids. These compounds have also been studied because of their intriguing spiro-lactone ring formation along with various modifications. Here, we present an extension of the original austinol/dehydroaustinol biosynthesis pathway from Aspergillus nidulans in the recently identified filamentous fungus Aspergillus calidoustus. Besides the discovery and elucidation of further derivatives, genome mining led to the discovery of new putative biosynthetic genes. The genes involved in the biosynthesis of later austinoid products were characterized, and among them was a second polyketide synthase gene in the A. calidoustus cluster that was unusual because it was a noninterative polyketide synthase producing a diketide. This diketide product was then loaded onto the austinoid backbone, resulting in a new insecticidal derivative, calidodehydroaustin.

中文翻译:

一个扩展Austinoid生物合成途径的发现在黑calidoustus

丝状真菌产生了广泛用于各种工业环境的天然产物(例如,药物和杀虫剂)。类萜由于其多种生物活性而成为人们关注的天然产物。在类胡萝卜素中,有一组称为奥斯汀的杀虫化合物。这些化合物还因其迷人的螺内酯环形成以及各种修饰而得到了研究。在这里,我们提出了从刚发现的丝状真菌Calidoustus的构巢曲霉中原始的奥斯丁醇/脱氢奥斯丁醇生物合成途径的扩展。。除了发现和阐明其他衍生物外,基因组挖掘还导致发现了新的假定生物合成基因。表征了后来的类奥斯汀产物的生物合成中涉及的基因,其中有一个在拟南芥簇中的第二个聚酮化合物合酶基因,这是不寻常的,因为它是产生二酮化合物的非交互性聚酮化合物合酶。然后将该双酮化合物产物装载到类奥斯汀骨架上,从而产生新的杀虫衍生物,calidodehydroaustin。
更新日期:2017-03-15
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