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Intertwined Precursor Supply during Biosynthesis of the Catecholate–Hydroxamate Siderophores Qinichelins in Streptomyces sp. MBT76
ACS Chemical Biology ( IF 4 ) Pub Date : 2017-10-02 00:00:00 , DOI: 10.1021/acschembio.7b00597
Jacob Gubbens 1 , Changsheng Wu 2 , Hua Zhu 2 , Dmitri V. Filippov 1 , Bogdan I. Florea 1 , Sébastien Rigali 3 , Herman S. Overkleeft 1 , Gilles P. van Wezel 2
Affiliation  

The explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe the discovery of a novel group of catecholate–hydroxamate siderophores termed qinichelins (25) from Streptomyces sp. MBT76. Correlation between the metabolite levels and the protein expression profiles identified the biosynthetic gene cluster (named qch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry, and NMR. The genome of Streptomyces sp. MBT76 contains three gene clusters for the production of catecholate–peptide siderophores, including a separate cluster for the production of a shared catecholate precursor. In addition, an operon in the qch cluster was identified for the production of the ornithine precursor for qinichelins, independent of primary metabolism. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.

中文翻译:

链霉菌属中邻苯二酚-羟基氨基甲酸酯基尼古林生物合成过程中的前体供应交错。MBT76

基因组测序的爆炸性增长和生物信息学工具的发展彻底改变了从放线菌中发现天然产物的原理。特别是,这表明放线菌基因组包含许多孤儿基因簇,这些簇可能具有指明许多尚未发现的生物活性专门代谢物的潜力,代表了巨大的未利用的化学多样性。在这里,我们描述了从链霉菌属物种中发现的一组称为儿茶素(25)的儿茶酚-异羟肟酸酯铁载体的发现。MBT76。代谢物水平与蛋白质表达谱之间的相关性确定了生物合成基因簇(命名为qch)最有可能负责qinichelin的生物合成。分子的结构已通过生物信息学,质谱和NMR进行了阐明。链霉菌的基因组。MBT76包含三个用于生产儿茶酚酸-肽铁载体的基因簇,包括一个用于生产共享的儿茶酚酸前体的单独的簇。另外,在qch簇中发现了一个操纵子,用于生产鸟胆素的鸟氨酸前体,而与初级代谢无关。这种生物合成的复杂性为科学家在将合成生物学方法应用于天然产物发现时面临的挑战提供了新的见解。
更新日期:2017-10-03
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