Zhanli Wang, Lu Han, Lei Gao*, Liyun Zhang, Yan Xie, Hanwu Liu, Junping Fan, Ming Wu, Ning Yue, Yan Wang, Meng Han, Tongcan Sun, Qi Ding, Xiyin Zheng, Jidong Cao, Xueqi Shen, Haijun Wang, Tuxunaili Aizitili, Chunyan Wu, Xuehong Wu, Zhenhua Liu, Yiguo Hong, Xiaoguang Lei*, and Yule Liu* Cell, Available online 8 May 2026 https://doi.org/10.1016/j.cell.2026.04.021 Phytoalexins are core components of plant chemical defense against pathogens. However, the genetic basis and regulatory mechanisms governing their biosynthesis remain preliminary. Debneyol is a well-defined, broad-spectrum fungicidal phytoalexin. Here, we elucidate its biosynthetic pathway, key regulators, and activity against multiple pathogens. We show that debneyol is synthesized from farnesyl pyrophosphate (FPP) through three steps catalyzed by 5-epi-aristolochene synthase (EAS), 5-epi-aristolochene epoxidase (EAE), and epoxide hydrolase-1 (EH1). MCD1 (miR1919-targeted cell death-factor-1) interacts with EAS and EAE, enhancing their association and EAE activity and promoting debneyol biosynthesis. Increased MCD1expression confers plant resistance not only against fungal but also viral and bacterial pathogens. Our work reveals a complete plant phytoalexin-based chemical defense machinery, opening avenues for engineering broad-spectrum plant resistance and industrial-scale debneyol production via synthetic biology.
Zhanli Wang, Lu Han, Lei Gao*, Liyun Zhang, Yan Xie, Hanwu Liu, Junping Fan, Ming Wu, Ning Yue, Yan Wang, Meng Han, Tongcan Sun, Qi Ding, Xiyin Zheng, Jidong Cao, Xueqi Shen, Haijun Wang, Tuxunaili Aizitili, Chunyan Wu, Xuehong Wu, Zhenhua Liu, Yiguo Hong, Xiaoguang Lei*, and Yule Liu*
Cell, Available online 8 May 2026
https://doi.org/10.1016/j.cell.2026.04.021
Phytoalexins are core components of plant chemical defense against pathogens. However, the genetic basis and regulatory mechanisms governing their biosynthesis remain preliminary. Debneyol is a well-defined, broad-spectrum fungicidal phytoalexin. Here, we elucidate its biosynthetic pathway, key regulators, and activity against multiple pathogens. We show that debneyol is synthesized from farnesyl pyrophosphate (FPP) through three steps catalyzed by 5-epi-aristolochene synthase (EAS), 5-epi-aristolochene epoxidase (EAE), and epoxide hydrolase-1 (EH1). MCD1 (miR1919-targeted cell death-factor-1) interacts with EAS and EAE, enhancing their association and EAE activity and promoting debneyol biosynthesis. Increased MCD1expression confers plant resistance not only against fungal but also viral and bacterial pathogens. Our work reveals a complete plant phytoalexin-based chemical defense machinery, opening avenues for engineering broad-spectrum plant resistance and industrial-scale debneyol production via synthetic biology.
