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从 t-22 中的一个 PKS-NRPS 编码基因簇中挖掘隐性四氢呋喃天然产物的基因组

Genome mining of cryptic tetronate natural products from a PKS-NRPS encoding gene cluster in t-22.

机构信息

Department of Chemical and Biomolecular Engineering, University of California Los Angeles, CA 90095, USA.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

出版信息

Org Biomol Chem. 2021 Mar 11;19(9):1985-1990. doi: 10.1039/d0ob02545c.

Abstract

Trichoderma harzianum is a widely used biocontrol agent in agriculture. Obtaining a full inventory of the small molecules that can be biosynthesized from the encoded biosynthetic gene clusters (BGCs) is therefore useful for understanding associated plant-microbe and microbe-microbe interactions. Here we heterologously reconstituted a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) encoding gene cluster from T. harzianum t-22 in Aspergillus nidulans A1145. Six new tetronate natural products trihazone A-F (1-6) were isolated and elucidated by HRESIMS and 1D and 2D NMR data. Three of the products contain an exocyclic olefin, which is derived from the oxidative decarboxylation of an α-ketoglutarate-dependent dioxygenase ThnC as shown by biochemical assays.

摘要

哈茨木霉是农业中广泛应用的一种生物防治剂。因此,获得可由编码生物合成基因簇(BGCs)生物合成的小分子的完整清单,有助于理解相关的植物-微生物和微生物-微生物相互作用。在这里,我们在 Aspergillus nidulans A1145 中异源重建了来自 T. harzianum t-22 的聚酮合酶-非核糖体肽合酶(PKS-NRPS)编码基因簇。通过高分辨率电喷雾质谱(HRESIMS)和 1D 和 2D NMR 数据,分离并阐明了六种新的四氢唑烷酮天然产物 trihazone A-F(1-6)。其中三种产物含有一个外环烯烃,这是由 ThnC 依赖的α-酮戊二酸双加氧酶的氧化脱羧作用产生的,这一结果通过生化实验得到证实。

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