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Improved Heterologous Production of the Nonribosomal Peptide-Polyketide Siderophore Yersiniabactin Through Metabolic Engineering and Induction Optimization

机译:通过代谢工程和诱导优化改善异源生产非核糖体多肽-聚酮化合物铁载体耶尔西菌素

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摘要

Biosynthesis of complex natural products like polyketides and nonribosomal peptides using Escherichia coli as a heterologous host provides an opportunity to access these molecules. The value in doing so stems from the fact that many compounds hold some therapeutic or other beneficial property and their original production hosts are intractable for a variety of reasons. In this work, metabolic engineering and induction variable optimization were used to increase production of the polyketide-nonribosomal peptide compound yersiniabactin, a siderophore that has been utilized to selectively remove metals from various solid and aqueous samples. Specifically, several precursor substrate support pathways were altered through gene expression and exogenous supplementation in order to boost production of the final compound. The gene expression induction process was also analyzed to identify the temperatures and inducer concentrations resulting in highest final production levels. When combined, yersiniabactin production was extended to similar to 175 mg L-1. (C) 2016 American Institute of Chemical Engineers
机译:使用大肠杆菌作为异源宿主生物合成复杂的天然产物(如聚酮化合物和非核糖体肽)提供了访问这些分子的机会。这样做的价值源于以下事实:许多化合物具有某些治疗或其他有益特性,并且由于各种原因,它们的原始生产宿主很难处理。在这项工作中,代谢工程和诱导变量优化被用来增加聚酮化合物-非核糖体肽化合物耶尔西菌素的产量,铁载体已被用于选择性地从各种固体和水性样品中去除金属。具体而言,通过基因表达和外源性补充改变了几种前体底物支持途径,以促进最终化合物的产生。还分析了基因表达诱导过程以鉴定导致最高最终生产水平的温度和诱导剂浓度。合并后,耶尔西菌素的生产量将扩大到类似于175 mg L-1。 (C)2016美国化学工程师学会

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