Multiplex modification of Escherichia coli for enhanced β-alanine biosynthesis through metabolic engineering

[Display omitted] •A heterologous panD was inserted into genome to obtain initial β-alanine producer.•Deletion of β-alanine uptake system significantly improved β-alanine yield.•Modification the glucose uptake system increased the β-alanine production.•Overexpression of heterologous panD and aspB fu...

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Bibliographic Details
Published in:Bioresource technology 2021-12, Vol.342, p.126050-126050, Article 126050
Main Authors: Wang, Pei, Zhou, Hai-Yan, Li, Bo, Ding, Wen-Qing, Liu, Zhi-Qiang, Zheng, Yu-Guo
Format: Article
Language:English
Subjects:
Amino donor
beta-Alanine
CRISPR interference system
Escherichia coli - genetics
Escherichia coli Proteins - genetics
Metabolic Engineering
Plasmids
β-Alanine
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Summary:[Display omitted] •A heterologous panD was inserted into genome to obtain initial β-alanine producer.•Deletion of β-alanine uptake system significantly improved β-alanine yield.•Modification the glucose uptake system increased the β-alanine production.•Overexpression of heterologous panD and aspB further increased β-alanine titer.•A 43.94 g/L β-alanine was obtained in fed-batch fermentation. β-Alanine is the only naturally occurring β-amino acid, widely used in the fine chemical and pharmaceutical fields. In this study, metabolic design strategies were attempted in Escherichia coli W3110 for enhancing β-alanine biosynthesis. Specifically, heterologous L-aspartate-α-decarboxylase was used, the aspartate kinase I and III involved in competitive pathways were down-regulated, the β-alanine uptake system was disrupted, the phosphoenolpyruvate carboxylase was overexpressed, and the isocitrate lyase repressor repressing glyoxylate cycle shunt was delete, the glucose uptake system was modified, and the regeneration of amino donor was up-regulated. On this basis, a plasmid harboring the heterologous panD and aspB was constructed. The resultant strain ALA17/pTrc99a-panDBS-aspBCG could yield 4.20 g/L β-alanine in shake flask and 43.94 g/L β-alanine (a yield of 0.20 g/g glucose) in 5-L bioreactor via fed-batch cultivation. These modification strategies were proved effective and the constructed β-alanine producer was a promising microbial cell factory for industrial production of β-alanine.
ISSN:0960-8524
1873-2976
DOI:10.1016/j.biortech.2021.126050