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<p>14-hydroxy-dehydroabietadiene is a precursor in biosynthesis pathway of triptolide in <i>Tripterygium wilfordii</i> and is vital for the production of triptolide and related diterpenes. The 14-hydroxy-dehydroabietadiene was produced in the engineered <i>Saccharomyces cerevisiae</i> WAT11 A-8 through expressing <i>SmMS</i>,<i> TwTPS9</i>, and <i>TwCYP82D274</i> in combination with <i>BTS1</i> and <i>ERG20</i>. The expression of <i>TwCPR3</i> in the <i>S. cerevisiae</i> A-9 and A-10 for providing the electron donating has no obvious role to elevate the production of 14-hydroxy-dehydroabietadiene, but the 14-hydroxy-dehydroabietadiene is 302.73&#xa0;µg L<sup>− 1</sup> after changing <i>S. cerevisiae</i> INVsc1 strain A-13, which is 1.64 times higher than <i>S. cerevisiae</i> initial engineered strain A-8. The fusion of <i>TwCYP82D274</i> and <i>TwCPR3</i> in INVsc1 strain A-14, the 14-hydroxy-dehydroabietadiene is 340.26&#xa0;µg L<sup>− 1</sup>, which is 1.85 times higher than strain A-8. After enhancing the acetyl-CoA metabolic flux, the 14-hydroxy-dehydroabietadiene is 508.01&#xa0;µg L<sup>− 1</sup> in INVsc1 strain A-15, which is 2.76 times higher than strain A-8. The 14-hydroxy-dehydroabietadiene is 612.76&#xa0;µg L<sup>− 1</sup> in INVsc1 strain A-16, which is 3.33 times higher than strain A-8 when overexpressing the truncated <i>tHMG1</i>. The YPDA medium was provided for engineered strain A-16 fermentation, the 14-hydroxy-dehydroabietadiene is 965.16&#xa0;µg L<sup>− 1</sup> in INVsc1 strain A-16, which is 5.24 times higher than strain A-8 in YPDA medium. These results provide a solid foundation for analyzing the biosynthesis pathway and the industrial-scale production of triptolide and related diterpenes.</p> Graphical Abstract <p></p>

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Efficient biosynthesis of the plant-derived diterpenoid 14-hydroxy-dehydroabietadiene in Saccharomyces cerevisiae

  • 期刊论文

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  • 发表日期：

    2026年1月19日

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  • Liu Kunhao,
  • Wang Xiaoli,
  • He Zedong,
  • Zhang Bin,
  • Ma Zhiqing,
  • Zhu Chuanshu

摘要

14-hydroxy-dehydroabietadiene is a precursor in biosynthesis pathway of triptolide in Tripterygium wilfordii and is vital for the production of triptolide and related diterpenes. The 14-hydroxy-dehydroabietadiene was produced in the engineered Saccharomyces cerevisiae WAT11 A-8 through expressing SmMS, TwTPS9, and TwCYP82D274 in combination with BTS1 and ERG20. The expression of TwCPR3 in the S. cerevisiae A-9 and A-10 for providing the electron donating has no obvious role to elevate the production of 14-hydroxy-dehydroabietadiene, but the 14-hydroxy-dehydroabietadiene is 302.73 µg L− 1 after changing S. cerevisiae INVsc1 strain A-13, which is 1.64 times higher than S. cerevisiae initial engineered strain A-8. The fusion of TwCYP82D274 and TwCPR3 in INVsc1 strain A-14, the 14-hydroxy-dehydroabietadiene is 340.26 µg L− 1, which is 1.85 times higher than strain A-8. After enhancing the acetyl-CoA metabolic flux, the 14-hydroxy-dehydroabietadiene is 508.01 µg L− 1 in INVsc1 strain A-15, which is 2.76 times higher than strain A-8. The 14-hydroxy-dehydroabietadiene is 612.76 µg L− 1 in INVsc1 strain A-16, which is 3.33 times higher than strain A-8 when overexpressing the truncated tHMG1. The YPDA medium was provided for engineered strain A-16 fermentation, the 14-hydroxy-dehydroabietadiene is 965.16 µg L− 1 in INVsc1 strain A-16, which is 5.24 times higher than strain A-8 in YPDA medium. These results provide a solid foundation for analyzing the biosynthesis pathway and the industrial-scale production of triptolide and related diterpenes.

Graphical Abstract