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