类表皮马酶-脱水酶复合体负责林亚里丁类核糖体的生物合成
Wanlu Xiao1, Takeshi Tsunoda2, Chitose Maruyama3
1Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan.
Bioscience, biotechnology, and biochemistry
|August 4, 2023
概括
研究人员确定了一种蛋白质复合体 (GrmH/GrmL),对于修改包括grisemycin在内的linaridin来说至关重要. 这种复合物催化了关键的脱水,表皮化和裂变步骤,即使与相关的前体.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 微生物学 微生物学
背景情况:
- 利纳里丁是通过核糖体合成的,具有独特的修饰,如脱丁氨酸和D-氨基酸.
- 利纳里丁的生物合成途径往往缺乏明显的脱水酶和表皮酶基因.
- 之前的研究表明,格里西米辛集群 (grm) 内的神秘基因对这些修改负责.
研究的目的:
- 确认两个拟议的基因grmH和grmL在灰胺生物合成中的功能.
- 阐明在线利丁生产中发生脱水,表皮化和蛋白质分解裂变的机制.
- 为了研究已识别的修改机器的基质特异性.
主要方法:
- 在Streptomyces lividans中的格里塞米辛生物合成基因集群的异质表达.
- 共同净化实验以确定GrmH和GrmL之间的蛋白质复合体形成.
- 在体内实验中评估GrmH和GrmL对于前体改性的必要性.
- 测试GrmH/GrmL复合物与相关的林纳里丁 (沙利尼佩普丁和西佩米辛) 的前体.
主要成果:
- GrmH和GrmL形成一个功能性蛋白质复合体.
- 无论是GrmH还是GrmL,都对灰素前体酸GrmA的脱水,表皮化和蛋白质分解裂变至关重要.
- 尽管氨基酸序列的变化,但GrmH/GrmL复合体对来自沙利尼佩普丁和西佩米辛的前体具有活性.
结论:
- GrmH/GrmL蛋白质复合体对格里西梅辛生物合成中的关键翻译后修饰负责.
- 这种复合体表现出一定程度的灵活性,可以容纳相关的利纳里丁前体.
- 这些发现为复杂天然产品的生物合成和潜在的工程策略提供了洞察力.
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