发现同通路酶揭示了一种协调生物合成的整个植物模型
bioRxiv : the preprint server for biology
|September 5, 2025
概括
研究人员发现了头素 (CET) 和同素 (HHT) 的生物合成途径,这两种化合物对于癌症治疗和研究至关重要. 这一发现为可持续生产这些有价值的植物性化物铺平了道路.
科学领域:
- 植物生物化学和分子生物学
- 自然产品的生物合成
- 药物发现和开发
背景情况:
- 荷莫哈林顿因 (HHT) 是FDA批准的白血病治疗和研究工具,它来自临灭绝的植物中发现的头素 (CET).
- 对于CET和HHT的生物合成途径尚不清楚,这阻碍了可持续生产的努力.
- 目前的HHT生产依赖于从植物中提取的CET的半合成,这引发了保护问题.
研究的目的:
- 阐明植物中头素 (CET) 和同素 (HHT) 的完整生物合成途径.
- 确定涉及CET和HHT生物合成的新基因和酶.
- 建立一个可持续的大规模生产HHT的基础.
主要方法:
- 与稳定同位素标记的前体养配对的非目标代谢量.
- 通过转录组学识别关键基因.
- 新型酶的表征,包括非正规的P450细胞染色体,非典型的短链脱酶和依赖2氧酸盐的二氧化酶.
主要成果:
- 在没有先前的中间体或基因知识的情况下,已经阐明了接近完整的生物合成途径.
- 发现了7种CET途径中间体和6种新生物合成酶.
- CET生物合成发生在根尖,而CET和HHT在整个植物中积累,这表明有协调的调节.
结论:
- 这项研究确定了CET支架的代谢途径,使未来的HHT可持续生产成为可能.
- 这些发现为*Cephalotaxus*物种的真核核糖体毒素生物合成提供了洞察力.
- 这项研究弥补了自然产品生物合成的关键知识差距, 对医学和保护有重大影响.
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