在天然产品生物合成中,假定终端化域的结构
Michael R Rankin1, Dheeraj Khare2, Lena Gerwick3
1Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
研究人员在细菌中特征了一种新的终端化域 (TAD). 这种酶域对于制造化天然产品至关重要,它结合NAD并具有催化氨酸,揭示了新的生物合成途径.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 细菌使用多基合成酶 (PKS) 和非核糖体合成酶 (NRPS) 生产有价值的天然产品.
- 标准的PKS/NRPS通路使用铁酶 (TE),但不能形成终端胺.
- 在产生化物产品的通路中存在无特征的终端域.
研究的目的:
- 描述假定终端化域 (TAD) 的结构和功能.
- 阐明TAD在天然产品生物合成中的催化机制.
- 调查TADs的分布和进化意义.
主要方法:
- 终端化域 (TAD) 的蛋白质结构确定.
- 生物化学测试以评估辅因子结合 (NAD) 和催化活性.
- 在细菌基因组中TAD分布的生物信息分析.
主要成果:
- 确定了TAD结构,揭示了催化氨酸残留物.
- TAD与NAD结合,尼古丁胺位于催化氨酸附近.
- 在结构上,TAD与蓝藻细菌的乙-ACP还原酶 (AAR) 有着相似之处.
- 在细菌中,TADs广泛存在,通常位于NRPS模块的终端.
结论:
- TAD是一种新的酶域,可催化细菌天然产品中末端胺的形成.
- 该机制涉及NAD结合和催化氨酸,类似于AAR.
- 化物天然产品的广泛分布表明,大量未被发现的化物天然产品等待发现.
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