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Induction of secondary metabolism of Aspergillus terreus ATCC 20542 in the batch bioreactor cultures

机译:批处理生物反应器培养物中土曲霉ATCC 20542的次级代谢诱导

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摘要

Cultivation of Aspergillus terreus ATCC 20542 in a stirred tank bioreactor was performed to induce the biosynthesis of secondary metabolites and provide the bioprocess-related insights into the metabolic capabilities of the investigated strain. The activation of biosynthetic routes was attempted by the diversification of process conditions and growth media. Several strategies were tested, including the addition of rapeseed oil or inulin, changing the concentration of nitrogen source, reduction of chlorine supply, cultivation under saline conditions, and using various aeration schemes. Fifteen secondary metabolites were identified in the course of the study by using ultra-high performance liquid chromatography coupled with mass spectrometry, namely mevinolinic acid, 4a,5-dihydromevinolinic acid, 3α-hydroxy-3,5-dihydromonacolin L acid, terrein, aspulvinone E, dihydroisoflavipucine, (+)-geodin, (+)-bisdechlorogeodin, (+)-erdin, asterric acid, butyrolactone I, desmethylsulochrin, questin, sulochrin, and demethylasterric acid. The study also presents the collection of mass spectra that can serve as a resource for future experiments. The growth in a salt-rich environment turned out to be strongly inhibitory for secondary metabolism and the formation of dense and compact pellets was observed. Generally, the addition of inulin, reducing the oxygen supply, and increasing the content of nitrogen source did not enhance the production of examined molecules. The most successful strategy involved the addition of rapeseed oil to the chlorine-deficient medium. Under these conditions, the highest levels of butyrolactone I, asterric acid, and mevinolinic acid were achieved and the presence of desmethylsulochrin and (+)-bisdechlorogeodin was detected in the broth. The constant and relatively high aeration rate in the idiophase was shown to be beneficial for terrein and (+)-geodin biosynthesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-015-7157-1) contains supplementary material, which is available to authorized users.
机译:在搅拌罐式生物反应器中进行了曲霉曲霉ATCC 20542的培养,以诱导次生代谢产物的生物合成,并为研究菌株的代谢能力提供了与生物过程相关的见解。通过多种工艺条件和生长培养基来尝试激活生物合成途径。测试了几种策略,包括添加菜籽油或菊粉,改变氮源浓度,减少氯气供应,在盐条件下培养以及使用各种曝气方案。在研究过程中,通过使用超高效液相色谱-质谱联用,鉴定了15种次级代谢产物,分别是甲羟萘甲酸,4a,5-二氢羟乙烯酸,3α-羟基-3,5-二氢monacolin L酸,terrein,aspulvinone E,二氢异黄酮维他命,(+)-大地精,(+)-双去氯geodin,(+)-erdin,阿魏酸,丁内酯I,去甲基磺基古丁菊酯,questin,磺胺古丁和去甲基戊二酸。该研究还提出了可以作为未来实验资源的质谱图。事实证明,在富含盐的环境中的生长强烈抑制了次级代谢,并观察到了致密和致密的沉淀物的形成。通常,添加菊粉,减少氧气的供应以及增加氮源的含量并不能提高所检查分子的产量。最成功的策略是将菜籽油添加到缺氯培养基中。在这些条件下,获得了最高水平的丁内酯I,戊酸和甲萘甲酸,并且在肉汤中检测到去甲基磺草菊素和(+)-双去氯geodin的存在。已证明在中期保持恒定且相对较高的曝气速率有利于Terrein和(+)-geodin的生物合成。电子补充材料本文的在线版本(doi:10.1007 / s00253-015-7157-1)包含补充材料,可供授权用户使用。

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