Haplotype-phased genome unveils the butylphthalide biosynthesis and homoploid hybrid origin of Ligusticum chuanxiong

文献类型： 外文期刊

第一作者： Nie, Bao

作者： Nie, Bao;Chen, Xueqing;Hou, Zhuangwei;Guo, Miaoxian;Li, Cheng;Sun, Wenkai;Ji, Jiaojiao;Zang, Lanlan;Yang, Song;Li, Wei;Wang, Li;Fan, Pengxiang;Zhang, Wenhao;Zhang, Wenhao;Li, Hang;Tan, Yuzhu;Wang, Li

作者机构：

期刊名称：SCIENCE ADVANCES （ 影响因子：13.6； 五年影响因子：15.4 ）

ISSN： 2375-2548

年卷期： 2024 年 10 卷 6 期

页码：

收录情况： SCI

摘要： Butylphthalide is one of the first-line drugs for ischemic stroke therapy, while no biosynthetic enzyme for butylphthalide has been reported. Here, we present a haplotype-resolved genome of Ligusticum chuanxiong, a long-cultivated and phthalide-rich medicinal plant in Apiaceae. On the basis of comprehensive screening, four Fe(II)- and 2-oxoglutarate-dependent dioxygenases and two CYPs were mined and further biochemically verified as phthalide C-4/C-5 desaturases (P4,5Ds) that effectively promoted the forming of (S)-3-n-butylphthalide and butylidenephthalide. The substrate promiscuity and functional redundancy featured for P4,5Ds may contribute to the high phthalide diversity in L. chuanxiong. Notably, comparative genomic evidence supported L. chuanxiong as a homoploid hybrid with Ligusticum sinense as a potential parent. The two haplotypes demonstrated exceptional structure variance and diverged around 3.42 million years ago. Our study is an icebreaker for the dissection of phthalide biosynthetic pathway and reveals the hybrid origin of L. chuanxiong, which will facilitate the metabolic engineering for (S)-3-n-butylphthalide production and breeding for L. chuanxiong.

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