Convergent evolution of berberine biosynthesis
Berberine is an effective antimicrobial and antidiabetic alkaloid, primarily extracted from divergent botanical lineages, specifically <i>Coptis</i> (Ranunculales, early-diverging eudicot) and <i>Phellodendron</i> (Sapindales, core eudicot). In comparison with its known pathway in <i>Coptis</i> species, its biosynthesis in <i>Phellodendron</i> species remains elusive. Using chromosome-level genome assembly, coexpression matrix, and biochemical assays, we identified six key steps in berberine biosynthesis from <i>Phellodendron amurense</i>, including methylation, hydroxylation, and berberine bridge formation. Notably, we discovered a specific class of <i>O</i>-methyltransferases (NOMT) responsible for <i>N</i>-methylation. Structural analysis and mutagenesis of PaNOMT9 revealed its unique substrate-binding conformation. In addition, unlike the classical FAD-dependent berberine bridge formation in Ranunculales, <i>Phellodendron</i> uses a NAD(P)H-dependent monooxygenase (PaCYP71BG29) for berberine bridge formation, originating from the neofunctionalization of tryptamine 5-hydroxylase. Together, these findings reveal the convergence of berberine biosynthesis between <i>Coptis</i> and <i>Phellodendron</i> and signify the role of the convergent evolution in plant specialized metabolisms.
Authors
- Ya Tian (ORCID: https://orcid.org/0000-0001-9482-4307)
- Chang Cao
- Yuanze Zhou (ORCID: https://orcid.org/0000-0002-8542-6048)
- Yuhong Zhang (ORCID: https://orcid.org/0000-0003-4230-5868)
- Chengpeng Fan (ORCID: https://orcid.org/0000-0001-9428-9463)
- Jingyuan Song (ORCID: https://orcid.org/0000-0003-2733-0416)
- Ziyan Xie (ORCID: https://orcid.org/0000-0002-1728-5001)
- Baozhong Duan (ORCID: https://orcid.org/0000-0002-9819-6050)
- Tingxia Liu
- Lingzhe Kong
- Wei Sun (ORCID: https://orcid.org/0000-0001-5675-0466)
- Zhichao Xu (ORCID: https://orcid.org/0000-0003-1753-5602)
- Ranran Gao (ORCID: https://orcid.org/0000-0002-7164-0289)
- Jiushi Liu (ORCID: https://orcid.org/0000-0003-2678-6155)
- Chengwei Liu (ORCID: https://orcid.org/0000-0003-2746-2080)
- Qi Li (ORCID: https://orcid.org/0000-0003-2564-7225)
- Lixia Tian (ORCID: https://orcid.org/0000-0002-9670-148X)
- Shilin Chen (ORCID: https://orcid.org/0000-0002-0449-236X)
- Zhoujie An (ORCID: https://orcid.org/0000-0002-1638-3179)
- Hui Yao (ORCID: https://orcid.org/0000-0002-1760-4420)
- Haitao Liu (ORCID: https://orcid.org/0009-0002-4342-3938)
- Jing Wang (ORCID: https://orcid.org/0000-0003-0942-5470)
- Wanran Zhang
- Baojiang Zheng
- Yifan Wang (ORCID: https://orcid.org/0009-0003-1339-1856)
- Yuwei Ma (ORCID: https://orcid.org/0009-0002-6692-1921)
Institutions
- Army Medical University (CN)
- Guizhou University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- State Administration of Traditional Chinese Medicine of the People's Republic of China (CN)
- Wuhan University (CN)
- Southwest Hospital (CN)
- Northeast Forestry University (CN)
- Chengdu University of Traditional Chinese Medicine (CN)
- Dali University (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1126/sciadv.ads3596
- Citations
- 30
- Primary Topic
- Berberine and alkaloids research
- Type
- article
- Field-Weighted Citation Impact
- 13.43