基于比较代谢组学的理性优化方法提高阿维菌素产量

发布时间：2018-05-26 11:49

本文选题：阿维链霉菌 + 阿维菌素　；参考：《微生物学报》2017年02期

【摘要】：【目的】利用比较代谢组学的分析方法,研究不同发酵培养基中阿维链霉菌的胞内代谢差异,揭示合成阿维菌素的关键代谢物和代谢途径,再通过理性优化添加主要关键代谢物,提高阿维菌素产量。【方法】对M1和M2培养基中生长的菌体进行基于GC-MS的胞内代谢组学分析,通过理性添加强化前体代谢物,确定阿维菌素高产培养基。【结果】GC-MS共检测到232种物质,能够精确匹配70种胞内代谢物,通过PCA和PLS分析,最终确定了21种已知的胞内代谢物与阿维菌素的生物合成密切相关。其中乳酸、丙酮酸、琥珀酸、苏氨酸、异亮氨酸、缬氨酸和油脂类物质对阿维菌素的产量影响较为显著。通过单独或组合优化添加这些前体,阿维菌素的产量从5.36 g/L提高到了5.92 g/L,增加了10.4%。【结论】基于比较代谢组学分析的理性优化培养基的方法可有效提高阿维菌素的产量,并为提高当下生物基产品的产量提供了新思路。
[Abstract]:[objective] to study the difference of intracellular metabolism of Streptomyces avermectin in different fermentation media by comparative metabolomics analysis, and to reveal the key metabolites and metabolic pathways for the synthesis of avermectin. The production of avermectin was increased by rational optimization of the main metabolites. [methods] the intracellular metabolites of the bacteria growing in M1 and M2 media were analyzed based on GC-MS, and the precursor metabolites were strengthened by rational addition. [results] A total of 232 substances were detected by GC-MS, and 70 intracellular metabolites were accurately matched. The results were analyzed by PCA and PLS. Finally, 21 known intracellular metabolites were determined to be closely related to the biosynthesis of avermectin. Among them, lactic acid, pyruvate, succinic acid, threonine, isoleucine, valine and grease substances had significant effects on the yield of avermectin. The yield of avermectin increased from 5.36 g / L to 5.92 g / L, increasing 10.4% by adding these precursors individually or in combination. [conclusion] the rational optimization of culture medium based on comparative metabolomics analysis can effectively increase the yield of avermectin. It also provides a new way to improve the production of biological-based products.
【作者单位】：工业发酵微生物教育部重点实验室天津科技大学生物工程学院;
【基金】：国家“973项目”(2013CB734004) 国家自然科学基金(31370075,31471725)~~
【分类号】：R978.1

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