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<p>Premature flowering in <i>Angelica sinensis</i> (Danggui) triggers severe declines in root yield and medicinal quality5 by reducing bioactive ferulic acid and promoting lignification. Ferulate 5-hydroxylase (F5H), a cytochrome P450 enzyme, drives metabolic flux toward lignin biosynthesis, but its regulatory network and functional dynamics during early flowering remain unresolved. Transcriptomic and functional analyses identified <i>AsF5H</i> (<i>As09G05225</i>) as a key gene upregulated in early-flowering plants, correlating with root lignin accumulation and ferulic acid depletion. Phylogenetic studies confirmed F5H functional conservation across Apiaceae species, while heterologous expression in yeast validated its enzymatic activity in converting ferulic acid to 5-hydroxyferulic acid. Structural modeling pinpointed three substrate-binding residues (ARG98, ALA115, PHE116) critical for regiospecific hydroxylation. Through correlation network analysis, we identified the AP2/ERF transcription factor AsAP2 (<i>As08G00463</i>) as a regulator of AsF5H and support this regulation with transient assay in tobacco. Our findings elucidate a molecular trade-off between lignification and medicinal compound accumulation, providing actionable targets for metabolic engineering or breeding programs to suppress premature flowering effects and enhance root quality in commercial Danggui cultivation.</p>

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AsAP2 transcriptionally activates ferulate 5-hydroxylase, diverting ferulic acid metabolism toward lignin biosynthesis in Angelica sinensis.

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月30日

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  • Zhuojia Wu,
  • Jintao Fang,
  • Qun Liu,
  • Ping Wang,
  • Zhongxu Zhu,
  • Tsan-Yu Chiu

摘要

Premature flowering in Angelica sinensis (Danggui) triggers severe declines in root yield and medicinal quality5 by reducing bioactive ferulic acid and promoting lignification. Ferulate 5-hydroxylase (F5H), a cytochrome P450 enzyme, drives metabolic flux toward lignin biosynthesis, but its regulatory network and functional dynamics during early flowering remain unresolved. Transcriptomic and functional analyses identified AsF5H (As09G05225) as a key gene upregulated in early-flowering plants, correlating with root lignin accumulation and ferulic acid depletion. Phylogenetic studies confirmed F5H functional conservation across Apiaceae species, while heterologous expression in yeast validated its enzymatic activity in converting ferulic acid to 5-hydroxyferulic acid. Structural modeling pinpointed three substrate-binding residues (ARG98, ALA115, PHE116) critical for regiospecific hydroxylation. Through correlation network analysis, we identified the AP2/ERF transcription factor AsAP2 (As08G00463) as a regulator of AsF5H and support this regulation with transient assay in tobacco. Our findings elucidate a molecular trade-off between lignification and medicinal compound accumulation, providing actionable targets for metabolic engineering or breeding programs to suppress premature flowering effects and enhance root quality in commercial Danggui cultivation.