双氢青蒿酸脱氢酶介导的青蒿素生物合成替代途径

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Zizheng Guo, Ying Zhou, Jiangqi Li, De Liu, Yuwen Huang, Yu Zhang, Rongmin Yu, Jianhua Zhu
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引用次数: 0

摘要

二氢青蒿酸(DHAA)通过自身氧化作用转化为抗疟药青蒿素(ART)。青蒿酸(AA)的高产量是通过工程酿酒酵母发酵实现的,AA可以通过化学合成的方式通过DHAA转化为ART。然而,目前还没有关于催化 AA 向 DHAA 转化的酶的报道。在这里,我们报告了一种来自黄花蒿的双氢青蒿酸脱氢酶(AaDHAADH),它能催化 AA 和 DHAA 之间的双向转化。通过定点突变获得了一个优化突变体 AaDHAADH(P26L),它对 AA 的活性是原始基因的 2.82 倍。利用目标优化基因 AaDHAADH (P26L),在 S. cerevisiae 中实现了 DHAA 的从头合成。此外,在 5 L 生物反应器中发酵工程化的 S. cerevisiae,可获得 3.97 g/L 的 DHAA。AaDHAADH 的发现为 ART 的生物合成提供了一条更方便、更高效的替代途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis

Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis

Dihydroartemisinic acid (DHAA) converts into antimalarial drug artemisinin (ART) by auto-oxidation. High production of artemisinic acid (AA) has been achieved by fermentation of engineered Saccharomyces cerevisiae, and AA can be converted into ART through DHAA by chemical synthesis. However, there is no enzyme reported to catalyze the conversion of AA to DHAA. Here, we report a dihydroartemisinic acid dehydrogenase (AaDHAADH) from Artemisia annua L, which catalyzes the bidirectional conversion between AA and DHAA. An optimized mutant AaDHAADH (P26L) is obtained through site-directed mutagenesis and its activity toward AA is 2.82 times that of the original gene. De novo synthesis of DHAA is achieved in S. cerevisiae using the targeted optimized gene AaDHAADH (P26L). Furthermore, 3.97 g/L of DHAA is obtained by fermentation of engineered S. cerevisiae in 5 L bioreactor. The discovery of AaDHAADH provides a more convenient and efficient alternative route for ART biosynthesis.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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