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Improved Production of Triostin A in Engineered Escherichia coli with Furnished Quinoxaline Chromophore by Design of Experiments in Small-Scale Culture

机译:通过设计小规模培养实验,改进的喹喔啉生色团在工程大肠杆菌中生产Triostin A的产量

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Proficient production of the antitumor agent triostin A was developed using engineered Escherichia coli(E.coli).The bacterium played host to 15 genes that encode integral biosynthetic proteins which were identified and cloned from Streptomyces lasaliensis.In this study,triostin A production was dramatically increased by more than 20-fold,13 mg/L,with the introduction of exogenous quinoxaline-2-carboxylic acid(QXC),the speculative starting unit for biosynthesis of triostin A.Conversely,de novo production of triostin A by means of high cell density fed-batch fermentation that is exclusive of exogenous QXC bore a modest amount of the antitumor agent.Noteworthy production of the biologically active molecule was achieved with small-scale cultivation and quantitative analysis of the product was accomplished with a liquid chromatography-mass spectrometer.This simple and speedy system could easily provide us with valuable information for maximizing the production titer.Our entirely heterologous production system also establishes a basis for the future use of E.coli for generation of novel bioactive compounds through tolerable precursor-directed biosynthesis.
机译:利用工程化的大肠杆菌(E.coli)开发了抗肿瘤剂曲ostin A的高效生产。该细菌充当了15个编码完整生物合成蛋白的基因的宿主,这些基因已从拉萨里链霉菌中鉴定和克隆。通过引入外源性喹喔啉-2-羧酸(QXC),Triostin A的生物合成的投机起始单元,其产量增加了20倍以上,为13 mg / L。相反,通过高纯度从头生产Triostin A不含外源QXC的细胞密度补料分批发酵含有适量的抗肿瘤剂。小规模培养可实现有价值的生物活性分子生产,液相色谱-质谱仪可对产物进行定量分析这个简单而快速的系统可以轻松地为我们提供有价值的信息,以最大程度地提高生产效价。的生产系统还为将来通过可耐受的前体定向生物合成产生新的生物活性化合物奠定了基础。

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