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非紫杉醇和紫杉醇积累培养物中保守途径与特化途径之间的界面

The Interface amongst Conserved and Specialized Pathways in Non-Paclitaxel and Paclitaxel Accumulating Cultures.

作者信息

McKee Michelle C, Wilson Sarah A, Roberts Susan C

机构信息

Biology & Biotechnology, Worcester Polytechnic Institute, Worcester, MA 01609, USA.

Chemical Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA.

出版信息

Metabolites. 2021 Oct 7;11(10):688. doi: 10.3390/metabo11100688.

Abstract

Plant cell cultures derived from are used to produce valuable metabolites like paclitaxel, a chemotherapeutic drug. Methyl jasmonate elicitation enhances paclitaxel accumulation, but also inhibits culture growth and increases phenylpropanoid biosynthesis, two side effects that detract from taxane accumulation. To understand the connection between all of these processes, a systems approach is applied to investigate cell-wide metabolism in . Non-paclitaxel and paclitaxel accumulating cultures were elicited over single and multi-generational periods, and subsequent changes in conserved and specialized metabolism were quantified. Methyl jasmonate typically resulted in decreased growth and increased metabolite content in paclitaxel accumulating cultures. Conversely, elicitation typically resulted in either no change or decrease in accumulation of metabolites in the non-paclitaxel accumulating cultures. In both sets of cultures, variability was seen in the response to methyl jasmonate across generations of cell growth. Consolidation of these data determined that paclitaxel accumulation and basal levels of phenolic and flavonoid compounds are indirectly correlated with aggregate size. These approaches assess alternative metabolic pathways that are linked to paclitaxel biosynthesis and provide a comprehensive strategy to both understand the relationship between conserved and specialized metabolism in plants and in the design of strategies to increase natural product yields in plant cell culture.

摘要

源自[具体植物名称未给出]的植物细胞培养物被用于生产诸如紫杉醇(一种化疗药物)等有价值的代谢产物。茉莉酸甲酯诱导可增强紫杉醇的积累,但也会抑制培养物生长并增加苯丙烷类生物合成,这两个副作用不利于紫杉烷的积累。为了理解所有这些过程之间的联系,采用系统方法来研究[具体植物名称未给出]的全细胞代谢。在单代和多代培养期间对不积累紫杉醇和积累紫杉醇的培养物进行诱导,并对保守代谢和特殊代谢随后的变化进行定量分析。茉莉酸甲酯通常会导致积累紫杉醇的培养物生长减缓且代谢物含量增加。相反,诱导通常会使不积累紫杉醇的培养物中代谢物的积累没有变化或减少。在这两组培养物中,在细胞生长的各代中对茉莉酸甲酯的反应都存在变异性。对这些数据的整合确定,紫杉醇的积累以及酚类和黄酮类化合物的基础水平与聚集体大小间接相关。这些方法评估了与紫杉醇生物合成相关的替代代谢途径,并提供了一种全面的策略,既能理解植物中保守代谢和特殊代谢之间的关系,又能用于设计提高植物细胞培养中天然产物产量的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04fc/8538509/5de8b2aadc3e/metabolites-11-00688-g001.jpg

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