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

• 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
• Format: Article
• Language: English
• 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
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-023-12911-8

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