细胞染色体P450采矿用于布法迪埃诺利德多样化
Xiaolai Lei1, Xiaozheng Wang1, Weiliang Xiong1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
研究人员确定了细胞染色体P450酶,可以产生具有抗瘤活性的新型布法迪化物. 这些酶使有价值的类固醇化合物的高效,特定于地点的合成成为可能.
科学领域:
- 生物化学和分子生物学
- 自然产品的合成自然产品的合成
- 药理学 药理学是指药理学的学科.
背景情况:
- 布法类固醇是具有显著心和抗瘤特性的类固醇,在传统中医中使用.
- 由于从中提取的成本昂贵,以及化学合成的困难,bufadienolides的获取能力有限.
- 需要有效的方法来生产具有特定修改的多种类型的bufadienolides.
研究的目的:
- 为了确定参与青中bufadienolide生物合成的酶.
- 开发一种生产新型和改性布法醇的方法.
- 为了评估新合成的bufadienolides的抗瘤潜力.
主要方法:
- 转录组和基因组分析以确定候选细胞P450 (CYP) 酶.
- 酵母活性以酵母为基础的选平台.
- 生产,结构识别和生物评估的bufadienolides.
主要成果:
- 八个CYP酶和一个真菌CYP (Sth10) 被确定为催化布法迪埃诺化.
- 产生了15种布法烯化物,包括6种新型化合物.
- 由CYP46A35产生的19-基布法林和1β-基布法林显示出强大的瘤细胞增殖抑制.
- CYP46A35 证明了增强的催化效率和扩大基质范围到孕激素和.
结论:
- 在的布法迪埃诺化合成中阐明关键的酶修饰.
- 开发一个有效的平台,用于网站特定的合成有价值的bufadienolides.
- 有潜力生产具有增强治疗作用的新型类固醇药物.
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