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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structure Elucidation And Biosynthesis Of Fuscachelins, Peptide Siderophores From The Moderate Thermophile Thermobifida Fusca
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Structure Elucidation And Biosynthesis Of Fuscachelins, Peptide Siderophores From The Moderate Thermophile Thermobifida Fusca

机译：Fuscachelins，中度嗜热嗜热菌Fusca的肽铁载体的结构解析和生物合成

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摘要

Bacteria belonging to the order Actinomycetales have proven to be an important source of biologically active and often therapeutically useful natural products. The characterization of orphan biosynthetic gene clusters is an emerging and valuable approach to the discovery of novel small molecules. Analysis of the recently sequenced genome of the thermophilic actinomycete Thermobifida fusca revealed an orphan nonribosomal peptide biosynthetic gene cluster coding for an unknown siderophore natural product. T. fusca is a model organism for the study of thermostable cellulases and is a major degrader of plant cell walls. Here, we report the isolation and structure elucidation of the fuscachelins, siderophore natural products produced by T. fusca. In addition, we report the purification and biochemical characterization of the termination module of the nonribosomal peptide synthetase. Biochemical analysis of adenylation domain specificity supports the assignment of this gene cluster as the producer of the fuscachelin siderophores. The proposed nonribosomal peptide biosynthetic pathway exhibits several atypical features, including a macrocyclizing thioesterase that produces a 10-membered cyclic dep-sipeptide and a nonlinear assembly line, resulting in the unique heterodimeric architecture of the siderophore natural product.
机译：事实证明，放线菌属的细菌是生物活性且通常在治疗上有用的天然产物的重要来源。孤儿生物合成基因簇的表征是发现新型小分子的新兴且有价值的方法。对嗜热放线菌Thermobifida fusca最近测序的基因组的分析揭示了一个孤儿的非核糖体肽生物合成基因簇，其编码未知的铁载体天然产物。 T. fusca是研究热稳定纤维素酶的模型生物，是植物细胞壁的主要降解剂。在这里，我们报告了fuscachelins，T。fusca生产的铁载体天然产物的分离和结构解析。此外，我们报告了非核糖体肽合成酶的终止模块的纯化和生化特性。腺苷酸化域特异性的生化分析支持将该基因簇指定为富斯卡林铁载体的产生者。拟议的非核糖体肽生物合成途径表现出一些非典型特征，包括产生10元环状dep-septeptide的大环硫酯酶和非线性装配线，从而形成铁载体天然产物的独特异二聚体结构。

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