Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli

	Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli
	Zhu, Xinna 1; Tan, Zaigao 1,2; Xu, Hongtao 1; Chen, Jing 1,3; Tang, Jinlei 1; Zhang, Xueli 1
刊名	METABOLIC ENGINEERING
	2014-07-01
卷号	24 页码:87-96
关键词	Succinate Reducing equivalent Pyruvate dehydrogenase Pentose phosphate pathway Transhydrogenase
英文摘要	Reducing equivalents are an important cofactor for efficient synthesis of target products. During metabolic evolution to improve succinate production in Escherichia coli strains, two reducing equivalent-conserving pathways were activated to increase succinate yield. The sensitivity of pyruvate dehydrogenase to NADH inhibition was eliminated by three nucleotide mutations in the lpdA gene. Pyruvate dehydrogenase activity increased under anaerobic conditions, which provided additional NADH. The pentose phosphate pathway and transhydrogenase were activated by increased activities of transketolase and soluble transhydrogenase SthA. These data suggest that more carbon flux went through the pentose phosphate pathway, thus leading to production of more reducing equivalent in the form of NADPH, which was then converted to NADH through soluble transhydrogenase for succinate production. Reverse metabolic engineering was further performed in a parent strain, which was not metabolically evolved, to verify the effects of activating these two reducing equivalent-conserving pathways for improving succinate yield. Activating pyruvate dehydrogenase increased succinate yield from 1.12 to 1.31 mol/mol, whereas activating the pentose phosphate pathway and transhydrogenase increased succinate yield from 1.12 to 1.33 mol/mol. Activating these two pathways in combination led to a succinate yield of 1.5 mol/mol (88% of theoretical maximum), suggesting that they exhibited a synergistic effect for improving succinate yield. (C) 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved,
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biotechnology & Applied Microbiology
研究领域[WOS]	Biotechnology & Applied Microbiology
关键词[WOS]	ENGINEERED STRAINS ; ETHANOL-PRODUCTION ; ACID PRODUCTION ; FERMENTATION ; GLUCOSE ; DEHYDROGENASE ; GENE ; K-12 ; NADH ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000338934300009
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/1417]
专题	天津工业生物技术研究所_微生物代谢工程张学礼_期刊论文
作者单位	1.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Key Lab Syst Microbial Biotechnol, Beijing 100864, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Xinna,Tan, Zaigao,Xu, Hongtao,et al. Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli[J]. METABOLIC ENGINEERING,2014,24:87-96.
APA	Zhu, Xinna,Tan, Zaigao,Xu, Hongtao,Chen, Jing,Tang, Jinlei,&Zhang, Xueli.(2014).Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli.METABOLIC ENGINEERING,24,87-96.
MLA	Zhu, Xinna,et al."Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli".METABOLIC ENGINEERING 24(2014):87-96.