The electron transport chain (ETC) is one of the major energy generation pathways in microorganisms under aerobic condition. Higher yield of ATP can be achieved through oxidative phosphorylation with consumption of NADH than with substrate level phosphorylation. However, most value‐added metabolites are in an electrochemically reduced state, which requires reducing equivalent NADH as a cofactor. Therefore, optimal production of value‐added metabolites should be balanced with ETC in terms of energy production. In this study, we attempted to reduce the activity of ETC to secure availability of NADH. The ETC mutants exhibited poor growth rate and production of fermentative metabolites compared to parental strain. Introduction of heterologous pathways for synthesis of 2,3‐butanediol and isobutanol to ETC mutants resulted in increased titres and yields of the metabolites. ETC mutants yielded higher NADH/NAD⁺ ratio but similar ATP content than that by the parental strain. Furthermore, ETC mutants operated fermentative metabolism pathways independent of oxygen supply in large‐scale fermenter, resulting in increased yield and titre of 2,3‐butanediol. Thus, engineering of ETC is a useful metabolic engineering approach for production of reduced metabolites.

中文翻译：

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通过工程化电子传输链改善大肠杆菌中2,3-丁二醇和异丁醇的生产

电子传输链（ETC）是有氧条件下微生物中主要的能量产生途径之一。通过消耗NADH的氧化磷酸化比通过底物水平的磷酸化可以实现更高的ATP收率。但是，大多数增值代谢物处于电化学还原状态，因此需要还原当量的NADH作为辅因子。因此，就能源生产而言，增值代谢物的最佳生产应与ETC保持平衡。在这项研究中，我们试图减少ETC的活性以确保NADH的可用性。与亲本菌株相比，ETC突变体显示出较差的生长速率和发酵代谢产物的产生。引入合成2的异源途径 3-丁二醇和异丁醇转化为ETC突变体会提高代谢物的滴度和收率。ETC突变体产生更高的NADH / NAD⁺比率，但ATP含量与亲本菌株相似。此外，在大型发酵罐中，ETC突变体的运转代谢途径与氧气供应无关，从而提高了2,3-丁二醇的产量和滴度。因此，ETC的工程设计是生产减少的代谢物的有用的代谢工程方法。