通过一种独特的ThDP依赖酶在异胺素中生物合成烯利丁前体
Yongjian Qiao1, Junbo Wang1, Dashan Zhang1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, China.
Synthetic and systems biotechnology
|September 12, 2024
概括
这项研究确定了siAniP作为一种新型的转基因酶,对于异素生物合成至关重要. 它催化了关键的凝结反应,使得新的无菌素类似物能够产生,具有潜在的抗真菌和杀虫剂应用.
科学领域:
- 生物化学和分子生物学
- 自然产品生物合成 自然产品生物合成
- 酶学 是一种酶学.
背景情况:
- anisomycin (化合物1) 是一种 pyrrolidine 抗生素,通过与核糖体结合来抑制蛋白质生物合成.
- 阿尼索米辛的帕拉甲基基是开发具有抗真菌和杀虫功能的类似物的一个关键结构特征.
- 在素生物合成中活性化和凝结烯酸的确切机制尚不清楚.
研究的目的:
- 阐明AniP和siAniP在异粒素 (化合物1) 生物合成中的作用.
- 描述siAniP的催化活性和基质特异性.
- 确定参与siAniP基质结合和催化功能的关键氨基酸残留物.
主要方法:
- 对阿尼索米辛生物合成基因 (aniP和siAniP) 的遗传操纵.
- 生物信息学分析用于预测酶功能.
- 酶测试以确定siAniP的催化活性,包括凝结反应.
- 结构分析,对接模型和现场定向突变发生,以确定关键的残留物.
主要成果:
- 遗传学研究证实了AniP和siAniP在异菌素生物合成中的重要作用.
- siAniP被确定为一种转基因酶,可催化4-基酸和甘甲的凝聚,从而启动罗利丁的合成.
- siAniP表现出对芳香基托酸的特异性和对各种化物的耐受性,使得不对称的分子间凝聚和α-基的形成成为可能.
- 关键残留物 (I220,H275,R322,W391) 被确定为siAniP基质结合的关键.
结论:
- siAniP是第一个用芳香基托酸催化C2基转移和对称分子间合的特征化转基托酶.
- 这些发现扩大了已知的跨基托酶和它们的催化能力.
- siAniP 是一种强大的生物催化剂,可以促进异素及其衍生物的结构创新,并有可能导致新的抗真菌和杀虫剂.
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