Efficient biosynthesis of 3-hydroxypropionic acid from glucose through multidimensional engineering of escherichia coli
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Date
2023
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Publisher
Elsevier Ltd
Abstract
3-Hydroxypropionic acid (3-HP) is a top value-added chemical with multifaceted application in chemical, material, and food field. However, limited availability of robust strains and elevated fermentation costs currently impose constraints on sustainable biosynthesis of 3-HP. Herein, transporter engineering, metabolic dynamic modulation, and enzyme engineering were combined to address above limitations. First, a glucose-utilizing 3-HP biosynthetic pathway was constructed in Escherichia coli, followed by recruiting alternative glucose transport system to overcome center metabolism overflow. Next, the Cra (a transcription factor)-dependent switch was applied to autonomously fine-tune carbon flux, which alleviated growth retardation and improved the 3-HP production. Subsequently, inactivation of glycerol facilitator (GlpF) increased intracellular glycerol levels and boosted 3-HP biosynthesis, but caused toxic intermediate 3-hydroxypropionaldehyde (3-HPA) accumulation. Furthermore, semi-rational design of aldehyde dehydrogenase (YdcW) increased its activity and eliminated 3-HPA accumulation. Finally, fed-batch fermentation of the final strain resulted in 52.73 g/L 3-HP, with a yield of 0.59 mol/mol glucose.
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Keywords
3-Hydroxypropionic acid, Biosynthesis, Enzyme semi-rational design, Glucose valorization, Multidimensional engineering
Citation
Zhang, Y., Yun, J., Zhang, G., Parvez, A., Zhou, L., Zabed, H.M., Li, J. and Qi, X., 2023. Efficient biosynthesis of 3-hydroxypropionic acid from glucose through multidimensional engineering of Escherichia coli. Bioresource Technology, 389, p.129822.