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Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement

文献类型： 外文期刊

作者： Wu, Junjun 1 ; Zhang, Xia 1 ; Zhou, Peng 1 ; Huang, Jiaying 1 ; Xia, Xiudong 2 ; Li, Wei 1 ; Zhou, Ziyu 1 ; Chen, Yue 1 ; Li 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Food Sci & Technol, 1 Weigang Rd, Nanjing 210095, Jiangsu, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Agroprod Proc, Nanjing 210095, Jiangsu, Peoples R China

关键词： β-oxidation reversal;ATP;NADH;Synthetic biology;Metabolic engineering

期刊名称：METABOLIC ENGINEERING （ 2020影响因子：9.783； 五年影响因子：9.566 ）

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收录情况： SCI

摘要： Abstract Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Highlights ? The highest metabolic efficiency of r-BOX was achieved. ? NADH was identified as a crucial determinant of process yield. ? Fermentative redox balance enabled maximum product synthesis. ? Two major factors limiting acetate reduction pathway were identified.

  • 相关文献

[1]A systematic optimization of medium chain fatty acid biosynthesis via the reverse beta-oxidation cycle in Escherichia coli. Wu, Junjun,Zhang, Xia,Dong, Mingsheng,Xia, Xiudong.

[2]宰后鸭肉骨骼肌细胞中凋亡的发生及其影响因素研究. 王道营,黄伟,张牧晗,刘芳,诸永志,徐幸莲,徐为民,曹建民. 2012

[3]Efficient de novo synthesis of resveratrol by metabolically engineered Escherichia coli. Wu, Junjun,Zhou, Peng,Zhang, Xia,Dong, Mingsheng,Wu, Junjun,Zhou, Peng,Zhang, Xia,Dong, Mingsheng.

[4]Exogenous ATP enhance signal response of suspension cells of transgenic rice (Oryza sativa L.) expressing maize C-4 -pepc encoded phosphoenolpyruvate carboxylase under PEG treatment. Huo, K.,Li, X.,He, Y. F.,Wei, X. D.,Zhao, C. F.,Wang, C. L.,Huo, K.,Lu, W..

[5]Photosynthetic characteristics and effect of ATP in transgenic rice with phosphoenolpyruvate carboxylase and pyruvate orthophosphate dikinase genes. Zhang, B. J.,Wang, R. F.,Zhang, B. J.,Ling, L. L.,Jiao, D. M.. 2009

[6]Stepwise modular pathway engineering of Escherichia coli for efficient one-step production of (2S)-pinocembrin. Wu, Junjun,Zhang, Xia,Dong, Mingsheng,Wu, Junjun,Zhou, Jingwen,Wu, Junjun,Zhang, Xia,Dong, Mingsheng.

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