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大肠杆菌氧化还原辅因子代谢工程
王白云1,2,3, 王晓玥1,2,3, 王智文*1,2,3, 陈涛1,2,3, 赵学明1,2,3
化学进展 ›› 2014, Vol. 26 ›› Issue (09) :1609-1618
大肠杆菌氧化还原辅因子代谢工程
王白云1,2,3, 王晓玥1,2,3, 王智文*1,2,3, 陈涛1,2,3, 赵学明1,2,3
化学进展 ›› 2014, Vol. 26 ›› Issue (09) :1609-1618
大肠杆菌氧化还原辅因子代谢工程
Redox Cofactor Metabolic Engineering with Escherichia coli
NAD+、NADP+、NADH、NADPH等四类烟酰胺类辅因子也被称为氧化还原辅因子，是维持细胞氧化还原平衡，驱动胞内许多分解与合成反应的重要分子。近年来，辅因子在生物转化系统中的作用受到研究者的重视，氧化还原辅因子更成为人们关注的重点。文章综述了大肠杆菌（Escherichia coli， E. coli）氧化还原辅因子代谢工程研究的最新进展，重点总结最近发展的氧化还原辅因子代谢工程策略，讨论不同代谢工程策略对细胞氧化还原辅因子水平的影响及其在生物合成中的应用，并展望了辅因子代谢工程未来发展方向。
Redox cofactor plays an important role in maintaining cellular redox balance and driving catabolic or anabolic reactions. As the driving force of biochemical reactions and redox carriers, redox cofactor has received much attention for enhancing biotransformation process in recent years. The Gram-negative bacterium Escherichia coli (E. coli) has been studied extensively on a fundamental and applied level and has become a predominant host microorganism for industrial applications. Metabolic engineering of E. coli for the enhanced biochemical production such as bioethanol, organic acids, biopolymer, complex natural compounds and so on, has been significantly promoted by the redox cofactor engineering. This review introduced various strategies to improve productivity and product titers by engineered E. coli through metabolic engineering pathways and key enzymes involved redox cofactor. Advanced metabolic engineering strategies in redox cofactor include metabolic engineering of pathway involved in NAD(P)H biosynthesis, mutual transformation of redox cofactor, expression of heterogeneous redox cofactor dependent enzymes, manipulation of pyridine biosynthesis and NAD+ transportation. These strategies have been successfully implemented in recombinant E. coli to increase cellular availability of desired redox cofactor or change cofactor specificity of key enzymes. While current cofactor strategies just focus on natural metabolic pathways and enzymes, novel strategy needs to be developed for manipulating redox cofactor completely according to the will of the human.
Contents
1 Introduction
2 Metabolic engineering of pathways involved in NAD(P)H biosynthesis
2.1 Pentose phosphate pathway
2.2 Glyoxylate bypass
2.3 Pyruvate metabolic pathway
3 Mutual transformation of redox cofactor
3.1 Transhydrogenase system
3.2 NAD+ kinase and NADH kinase
4 Expression of Heterogeneous redox cofactor dependent enzymes
4.1 Heterogeneous NAD(P)+-dependent enzymes
4.2 Heterogeneous NAD(P)H-dependent enzymes
5 Manipulation of pyridine biosynthesis and NAD+ transportation
6 Perspectives
redox cofactor
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