A synthetic biology approach based on genome mining and heterologous biosynthesis is a powerful tool for discovering novel natural products from a tremendous gene resource. We carried out fungal genome mining guided by a polyketide synthase gene using a public database and found a putative macrolide biosynthetic gene cluster with a highly reducing polyketide synthase gene and a thioesterase gene in Macrophomina phaseolina. Reconstitution of the cluster in Aspergillus oryzae, a model heterologous host for fungal natural product biosynthesis, produced a new 12-membered macrolide, phaseolide A. The absolute stereochemistry was elucidated by vibrational circular dichroism spectroscopy and the crystalline sponge method.

中文翻译：

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基于合成生物学的菜豆大环藻真菌大环内酯类化合物的发现。

基于基因组挖掘和异源生物合成的合成生物学方法是从巨大的基因资源中发现新的天然产物的强大工具。我们利用公共数据库在聚酮化合物合酶基因的指导下进行了真菌基因组挖掘，发现了一个假定的大环内酯生物合成基因簇，该聚类化合物在菜豆大孔菌中具有高度还原的聚酮化合物合酶基因和硫酯酶基因。在真菌天然产物生物合成的模型异源宿主米曲霉中重组簇，产生了新的12元大环内酯类，菜豆内酯A。通过振动圆二色性光谱和结晶海绵法阐明了绝对立体化学。