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Research Progress of Microbial Cofactor Engineering |
ZHANG Hong-wei,WANG Peng-chao() |
School of Life Sciences, Northeast Forestry University, Harbin 150040, China |
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Abstract Various cofactors are required in the process of most enzyme-catalyzed reaction of cells. Cofactor balance is very important to maintain the homeostasis of biochemical reaction in cells. However, insufficient supply of cofactors will lead to the disorder of cell growth and compound production. In recent years, the key role of cofactors in the biochemical reaction process has attracted the attention of researchers, but most cofactors are expensive and have poor stability. These disadvantages have limited the potential application of cofactor engineering. The development of synthetic biology and metabolic engineering provides feasible solutions for the sustainable supply of cofactors, and multiple strategies to strengthen the supply of cofactors effectively promote the biosynthesis of target compounds. Among them, nicotinamide cofactors NAD(P)+ and NAD(P)H are the most common redox cofactors in the process of microbial metabolism. They are important electron receptors or donors in all organisms, promote synthesis and catabolism reactions, and play a decisive role in maintaining the dynamic balance of intracellular redox. Starting from the main sources of NAD(P)H and the influence of NAD(P)+/NAD(P)H balance in the synthesis of natural products, cofactor engineering strategies were reviewed from three different dimensions. This paper introduces the latest research progress and application of multiple cofactor regeneration strategies through metabolic pathway regulation, introduction of exogenous oxidoreductase, and protein engineering. The future development prospects of cofactor metabolic engineering in biosynthesis is also discussed.
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Received: 14 November 2022
Published: 04 May 2023
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