自然产品生物合成中的假定终端化域的结构
bioRxiv : the preprint server for biology
|November 18, 2024
概括
研究人员在细菌中特征了一种新的终端化域 (TAD). 这个域结合NAD,在产生化天然产品方面起着催化作用,扩大了已知的多基基合成酶和非核糖体合成酶的化学结构.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 发现自然产品的发现
背景情况:
- 细菌使用模块化多基合成酶 (PKS) 和非核糖体合成酶 (NRPS) 生产有价值的天然产品.
- 这些系统通常使用铁酶 (TE) 域来释放产品,但对于具有终端胺键的产品,需要使用替代机制.
- 几条产生化物产品的通路都含有未表征的终端域.
研究的目的:
- 描述自然产品生物合成中所涉及的未经表征的终端域的结构和功能.
- 阐明这种新领域的催化机制和辅因子结合.
主要方法:
- 蛋白质结构的确定 (X射线结晶学).
- 生物化学测试以评估辅因子结合和催化活性.
- 对域分布和进化关系的生物信息分析.
主要成果:
- 确定了假定终端化域 (TAD) 的结构.
- TAD与NAD+结合,尼古丁胺位于不变的氨酸残留物附近.
- 这种囊可以被载体蛋白中间体所接触,这表明它在化中起着催化作用.
- 在结构上,TAD与蓝藻细菌的乙-ACP还原酶 (AAR) 有着相似之处.
- 生物信息分析表明,TAD在细菌中广泛存在,通常与NRPS模块相关.
结论:
- 终端化域 (TAD) 是一种参与细菌天然产物生物合成的新型催化域.
- TAD利用NAD+和一种催化氨酸来促进产品中终端胺键的形成.
- 对TAD的发现扩大了我们对NRPS/PKS化学的理解,并表明了大量未被发现的化物天然产品的储备.
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