在需要时使用直角的氧化还原辅因子调动氧化还原反应平衡
Derek Aspacio1, Yulai Zhang1, Youtian Cui2
1Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Nature chemical biology
|August 13, 2024
概括
研究人员开发了使用尼古丁胺胺单核酸 (NMN+) 作为氧化还原辅因子的新型生物催化剂. 这项创新允许在生物制造中独立控制氧化还原反应,将其与细胞代谢脱.
科学领域:
- 生物技术和合成生物学
- 酶工程是什么? 酶工程是什么?
- 代谢工程是代谢工程.
背景情况:
- 大自然利用尼古丁胺氨基二核酸 (NAD+) 和尼古丁胺氨基二核酸 (NADP+) 作为主要的氧化还原辅因子,具有明显的还原潜力,驱动催化和合成.
- 生物制造需要灵活控制氧化还原反应方向,独立于原生代谢途径.
研究的目的:
- 为了建立尼古丁胺胺单核酸 (NMN+) 作为一个非正规的配因子,与NAD (((P) +对应,用于脱的氧化还原控制.
- 开发一套工具来调节NMN+/NMNH比率,从而实现新的生物催化应用.
主要方法:
- 设计了一个减少的NMN+ (NMNH) 特定氧化酶 (Nox Ortho) 和一个NMN+ 特定的葡萄糖脱酶 (GDH Ortho).
- 应用了酶工程和建模原理,以创建具有高辅助因子特异性的NMN(H) 直角生物催化剂.
- 在无细胞系统和大肠杆菌中生产2,3-butanediol的组装工程酶.
主要成果:
- 开发的NMN(H) 正角生物催化剂表现出~10^3-10^6倍的辅因子特异性切换从NAD(P) +到NMN+.
- 通过使用工程系统成功生产了立体纯度的2,3-butanediol,证明了脱的氧化还原控制.
- 建立了一个强大的工具包,用于精确操纵NMNH:NMN+比率.
结论:
- 尼古丁胺胺单核酸 (NMN+) 作为一种多功能,非正规的辅助因子,用于生物制造中的正交氧还原控制.
- 开发的NMN(H) 直角生物催化剂和工具包在设计合成代谢途径方面提供了前所未有的灵活性.
- 这种方法将氧还原比与原生NAD (H) 和NADP (H) 池脱,为先进的生物生产策略铺平了道路.
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