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首页> 外文期刊>Biotechnology Progress >Improved Heterologous Erythromycin A Production through Expression Plasmid Re-design
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Improved Heterologous Erythromycin A Production through Expression Plasmid Re-design

机译：通过重新设计表达质粒改善异源红霉素A的生产

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摘要

The production of complex compounds from technically convenient microorganisms is an emerging route to the chemical diversity found in the surrounding environment. In this study, the antibiotic compound erythromycin A is produced from Escherichia coli as an alternative to native production through the soil bacterium Saccharopolyspora erythraea. By doing so, there is an opportunity to apply and refine engineering strategies for the manipulation of the erythromycin biosynthetic pathway and for the overproduction of this and other complex natural compounds. Previously, E. coli-derived production was enabled by the introduction of the entire erythromycin pathway (20 genes total) using separately selectable expression plas-mids which demonstrated negative effects on final biosynthesis through metabolic burden and plasmid instability. In this study, improvements to final production were made by altering the design of the expression plasmids needed for biosynthetic pathway introduction. Specifically, the total number of genes and plasmids was pruned to reduce both metabolic burden and plasmid instability. Further, a comparison was conducted between species-specific (E. coli vs. S. coelicolor) protein chaperonins. Results indicate improvements in growth and plasmid retention metrics. The newly designed expression platform also increased erythromycin A production levels 5-fold. In conclusion, the steps outlined in this report were designed to upgrade the E. coli erythromycin A production system, led to improved final compound titers, and suggest additional forms of pathway engineering to further improve results from heterologous production attempts.
机译：由技术上方便的微生物生产复杂的化合物是在周围环境中发现化学多样性的新兴途径。在这项研究中，抗生素化合物红霉素A是由大肠杆菌生产的，作为通过土壤细菌红多孢菌（Saccharopolyspora erythraea）天然生产的替代方法。这样，就有机会应用和完善工程策略来操纵红霉素的生物合成途径，以及过量生产这种和其他复杂的天然化合物。以前，通过使用单独选择的表达质粒引入完整的红霉素途径（总共20个基因），可以实现大肠杆菌衍生的生产，这些质粒通过代谢负担和质粒不稳定性显示出对最终生物合成的负面影响。在这项研究中，通过改变生物合成途径引入所需的表达质粒的设计，对最终生产进行了改进。具体而言，修剪基因和质粒的总数以减少代谢负担和质粒不稳定性。此外，在物种特异性（大肠杆菌与天蓝色链霉菌）蛋白伴侣蛋白之间进行了比较。结果表明生长和质粒保留指标的改善。新设计的表达平台还使红霉素A的生产水平提高了5倍。总之，本报告中概述的步骤旨在升级大肠杆菌红霉素A的生产系统，从而提高最终化合物的效价，并提出途径工程的其他形式，以进一步改善来自异源生产尝试的结果。

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