Systemic metabolic engineering of Enterobacter aerogenes for efficient 2,3-butanediol production.
Systemic metabolic engineering of Enterobacter aerogenes for efficient 2,3-butanediol production.
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产气肠杆菌系统代谢工程高效生产2，3-丁二醇
DOI：
10.1007/s00253-023-12911-8
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发表时间：
2024-01-19
影响因子：
5
通讯作者：
Zhao, Hongxin
中科院分区：
文献类型：
--
作者：
Lu, Ping;Bai, Ruoxuan;Gao, Ting;Chen, Jiale;Jiang, Ke;Zhu, Yalun;Lu, Ye;Zhang, Shuting;Xu, Fangxu;Zhao, Hongxin
2，3-丁二醇（2，3-BDO）是许多化学衍生物的重要门户分子。目前，微生物生产逐渐被认为是石油化学合成的绿色和可持续的替代品，但微生物2，3-BD 0的滴度、产率和生产率仍然不理想。在这里，我们使用系统性代谢工程策略来解除产气肠杆菌中2，3-BDO生产的瓶颈。首先，通过删除用于副产物合成的基因来重建丙酮酸代谢网络，以提高朝向2，3-BDO合成的通量，这导致产物滴度增加90%。其次，由于DR 1558的异源表达，提高了细胞对非生物胁迫的抗性，IAM 1183-LPCT/D的2，3-BDO产量提高了55%。第三，对碳源进行优化，进一步提高目标产物的收率。以蔗糖为原料，发酵液中2，3-BDO的效价最高，比葡萄糖高20%，产量达到0.49 g/g。最终，在5L发酵罐中，该菌株2，3-BDO的效价达到22.93g/L，比野生型菌株提高了85%，且除乙醇外，副产物的效价很低。E.产气菌提高了2，3-BDO的产量通过调节代谢通量，2，3-BDO的滴度提高了90%。表达响应调节剂DR 1558以提高2，3-BDO的产量。在线版本包含补充材料，可在10. 1007/s 00253 -023-12911-8获得。
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. 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 The online version contains supplementary material available at 10.1007/s00253-023-12911-8.
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影响因子：
5.2
作者：
通讯作者：
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影响因子：
6.3
作者：
Guo X;Cao C;Wang Y;Li C;Wu M;Chen Y;Zhang C;Pei H;Xiao D
通讯作者：
Xiao D
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影响因子：
8.3
作者：
Gao, Shuang;Li, Zhiling;Huang, Cong
通讯作者：
Huang, Cong
影响因子：
4.7
作者：
Chu, Wanying;Jiang, Ke;Zhao, Hongxin
通讯作者：
Zhao, Hongxin
影响因子：
8.4
作者：
Liang, Liya;Liu, Rongming;Gill, Ryan T.
通讯作者：
Gill, Ryan T.