You Chun, Huang Rui, Wei Xinlei, Zhu Zhiguang, Zhang Yi-Heng Percival
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin Airport Economic Area, Tianjin, 300308, People's Republic of China.
Biological Systems Engineering Department, Virginia Tech, 304 Seitz Hall, Blacksburg, VA 24061, USA.
Synth Syst Biotechnol. 2017 Oct 6;2(3):208-218. doi: 10.1016/j.synbio.2017.09.002. eCollection 2017 Sep.
Two natural nicotinamide-based coenzymes (NAD and NADP) are indispensably required by the vast majority of oxidoreductases for catabolism and anabolism, respectively. Most NAD(P)-dependent oxidoreductases prefer one coenzyme as an electron acceptor or donor to the other depending on their different metabolic roles. This coenzyme preference associated with coenzyme imbalance presents some challenges for the construction of high-efficiency and synthetic biology pathways. Changing the coenzyme preference of NAD(P)-dependent oxidoreductases is an important area of protein engineering, which is closely related to product-oriented synthetic biology projects. This review focuses on the methodology of nicotinamide-based coenzyme engineering, with its application in improving product yields and decreasing production costs. Biomimetic nicotinamide-containing coenzymes have been proposed to replace natural coenzymes because they are more stable and less costly than natural coenzymes. Recent advances in the switching of coenzyme preference from natural to biomimetic coenzymes are also covered in this review. Engineering coenzyme preferences from natural to biomimetic coenzymes has become an important direction for coenzyme engineering, especially for synthetic pathways and bioorthogonal redox pathways.
两种基于烟酰胺的天然辅酶（NAD和NADP）分别是绝大多数氧化还原酶进行分解代谢和合成代谢必不可少的物质。大多数依赖NAD(P)的氧化还原酶根据其不同的代谢作用，更倾向于将一种辅酶作为电子受体或供体而非另一种。这种与辅酶失衡相关的辅酶偏好给高效合成生物学途径的构建带来了一些挑战。改变依赖NAD(P)的氧化还原酶的辅酶偏好是蛋白质工程的一个重要领域，这与以产品为导向的合成生物学项目密切相关。本综述重点关注基于烟酰胺的辅酶工程方法及其在提高产品产量和降低生产成本方面的应用。已提出含烟酰胺的仿生辅酶来替代天然辅酶，因为它们比天然辅酶更稳定且成本更低。本综述还涵盖了辅酶偏好从天然辅酶向仿生辅酶转变的最新进展。将辅酶偏好从天然辅酶工程改造为仿生辅酶已成为辅酶工程的一个重要方向，特别是对于合成途径和生物正交氧化还原途径而言。
