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Systemic metabolic engineering of Enterobacter aerogenes for efficient 2,3-butanediol production

2,3-Butanediol (2,3-BDO) is an important gateway molecule for many chemical derivatives. Currently, microbial production is gradually being recognized as a green and sustainable alternative to petrochemical synthesis, but the titer, yield, and productivity of microbial 2,3-BDO remain suboptimal. Her...

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Published in:Applied microbiology and biotechnology 2024-12, Vol.108 (1), p.146-146, Article 146
Main Authors: Lu, Ping, Bai, Ruoxuan, Gao, Ting, Chen, Jiale, Jiang, Ke, Zhu, Yalun, Lu, Ye, Zhang, Shuting, Xu, Fangxu, Zhao, Hongxin
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container_title Applied microbiology and biotechnology
container_volume 108
creator Lu, Ping
Bai, Ruoxuan
Gao, Ting
Chen, Jiale
Jiang, Ke
Zhu, Yalun
Lu, Ye
Zhang, Shuting
Xu, Fangxu
Zhao, Hongxin
description 2,3-Butanediol (2,3-BDO) is an important gateway molecule for many chemical derivatives. Currently, microbial production is gradually being recognized as a green and sustainable alternative to petrochemical synthesis, but the titer, yield, and productivity of microbial 2,3-BDO remain suboptimal. Here, we used systemic metabolic engineering strategies to debottleneck the 2,3-BDO production in Enterobacter aerogenes . Firstly, the pyruvate metabolic network was reconstructed by deleting genes for by-product synthesis to improve the flux toward 2,3-BDO synthesis, which resulted in a 90% increase of the product titer. Secondly, the 2,3-BDO productivity of the IAM1183-LPCT/D was increased by 55% due to the heterologous expression of DR1558 which boosted cell resistance to abiotic stress. Thirdly, carbon sources were optimized to further improve the yield of target products. The IAM1183-LPCT/D showed the highest titer of 2,3-BDO from sucrose, 20% higher than that from glucose, and the yield of 2,3-BDO reached 0.49 g/g. Finally, the titer of 2,3-BDO of IAM1183-LPCT/D in a 5-L fermenter reached 22.93 g/L, 85% higher than the wild-type strain, and the titer of by-products except ethanol was very low. Key points Deletion of five key genes in E. aerogenes improved 2,3-BDO production The titer of 2,3-BDO was increased by 90% by regulating metabolic flux Response regulator DR1558 was expressed to increase 2,3-BDO productivity Graphical abstract
doi_str_mv 10.1007/s00253-023-12911-8
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Currently, microbial production is gradually being recognized as a green and sustainable alternative to petrochemical synthesis, but the titer, yield, and productivity of microbial 2,3-BDO remain suboptimal. Here, we used systemic metabolic engineering strategies to debottleneck the 2,3-BDO production in Enterobacter aerogenes . Firstly, the pyruvate metabolic network was reconstructed by deleting genes for by-product synthesis to improve the flux toward 2,3-BDO synthesis, which resulted in a 90% increase of the product titer. Secondly, the 2,3-BDO productivity of the IAM1183-LPCT/D was increased by 55% due to the heterologous expression of DR1558 which boosted cell resistance to abiotic stress. Thirdly, carbon sources were optimized to further improve the yield of target products. The IAM1183-LPCT/D showed the highest titer of 2,3-BDO from sucrose, 20% higher than that from glucose, and the yield of 2,3-BDO reached 0.49 g/g. Finally, the titer of 2,3-BDO of IAM1183-LPCT/D in a 5-L fermenter reached 22.93 g/L, 85% higher than the wild-type strain, and the titer of by-products except ethanol was very low. 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Finally, the titer of 2,3-BDO of IAM1183-LPCT/D in a 5-L fermenter reached 22.93 g/L, 85% higher than the wild-type strain, and the titer of by-products except ethanol was very low. Key points Deletion of five key genes in E. aerogenes improved 2,3-BDO production The titer of 2,3-BDO was increased by 90% by regulating metabolic flux Response regulator DR1558 was expressed to increase 2,3-BDO productivity Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38240862</pmid><doi>10.1007/s00253-023-12911-8</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5238-506X</orcidid><oa>free_for_read</oa></addata></record>
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subjects Aerogenes
Bioenergy and Biofuels
Biomedical and Life Sciences
Bioreactors
Biotechnology
Butanediol
Butylene Glycols - metabolism
Byproducts
Carbon sources
Enterobacter aerogenes
Enterobacter aerogenes - genetics
Enterobacter aerogenes - metabolism
Ethanol
Fermentation
Genes
Life Sciences
Metabolic engineering
Metabolic Engineering - methods
Metabolic flux
Metabolic networks
Metabolism
Microbial Genetics and Genomics
Microbiology
Microorganisms
Petrochemicals
Productivity
Pyruvic acid
Sucrose
Synthesis
title Systemic metabolic engineering of Enterobacter aerogenes for efficient 2,3-butanediol production
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