Journal
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
Volume 45, Issue 5, Pages 313-327Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s10295-018-2031-7
Keywords
Cofactor engineering; Redox balance; Metabolic engineering; Cofactor specificity; Synthetic biology
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Funding
- National Key Research and Development Project of China [2017YFD0201400]
- National Natural Science Foundation of China [31570089, 31170076]
- Funds for Creative Research Groups of China [21621004]
- New Century Outstanding Talent Support Program, Education Ministry of China
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NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.
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