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<p>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 <i>Saccharomyces cerevisiae</i>, 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 (<i>Aa</i>DHAADH) from <i>Artemisia annua</i> L, which catalyzes the bidirectional conversion between AA and DHAA. An optimized mutant <i>Aa</i>DHAADH (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 <i>S. cerevisiae</i> using the targeted optimized gene <i>AaDHAADH (P26L)</i>. Furthermore, 3.97 g/L of DHAA is obtained by fermentation of engineered <i>S. cerevisiae</i> in 5 L bioreactor. The discovery of <i>Aa</i>DHAADH provides a more convenient and efficient alternative route for ART biosynthesis.</p>

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Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月24日

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  • Zizheng Guo,
  • Ying Zhou,
  • Jiangqi Li,
  • De Liu,
  • Yuwen Huang,
  • Yu Zhang,
  • Rongmin Yu,
  • Jianhua Zhu

摘要

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.