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在.中过表达镁转运蛋白以生产高水平琥珀酸。

High-level succinic acid production by overexpressing a magnesium transporter in .

机构信息

Metabolic and Biomolecular Engineering National Research Laboratory and Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, Department of Chemical and Biomolecular Engineering (BK21 four), Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.

BioInformatics Research Center and BioProcess Engineering Research Center, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.

出版信息

Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2407455121. doi: 10.1073/pnas.2407455121. Epub 2024 Sep 6.

DOI:10.1073/pnas.2407455121
PMID:39240971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11406231/
Abstract

Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered . Although the importance of magnesium (Mg) ion on SA production has been evident from our previous studies, the role of Mg ion remains largely unexplored. In this study, we investigated the impact of Mg ion on SA production and developed a hyper-SA producing strain of by reconstructing the Mg ion transport system. To achieve this, optimal alkaline neutralizer comprising Mg ion was developed and the physiological effect of Mg ion was analyzed. Subsequently, the Mg ion transport system was reconstructed by introducing an efficient Mg ion transporter from . A high-inoculum fed-batch fermentation of the final engineered strain produced 152.23 ± 0.99 g/L of SA, with a maximum productivity of 39.64 ± 0.69 g/L/h. These findings highlight the importance of Mg ions and transportation system optimization in succinic acid production by .

摘要

琥珀酸(SA)是一种具有工业重要性的二羧酸,可以通过代谢工程高效生产。尽管镁(Mg)离子对 SA 生产的重要性已在我们之前的研究中得到证实,但 Mg 离子的作用在很大程度上仍未得到探索。在这项研究中,我们研究了 Mg 离子对 SA 生产的影响,并通过重建 Mg 离子运输系统,开发了一种高产 SA 的 工程菌。为此,开发了包含 Mg 离子的最佳碱性中和剂,并分析了 Mg 离子的生理效应。随后,通过从 引入高效的 Mg 离子转运蛋白,重建了 Mg 离子运输系统。最终工程菌的高接种量分批发酵生产了 152.23 ± 0.99 g/L 的 SA,最大比生产速率为 39.64 ± 0.69 g/L/h。这些发现强调了 Mg 离子和运输系统优化在 生产琥珀酸中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/adf44652a9a0/pnas.2407455121fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/db077e1ec258/pnas.2407455121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/7853cb81688b/pnas.2407455121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/264c36d5f322/pnas.2407455121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/4ff16fca740d/pnas.2407455121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/d30adf674365/pnas.2407455121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/adf44652a9a0/pnas.2407455121fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/db077e1ec258/pnas.2407455121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/7853cb81688b/pnas.2407455121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/264c36d5f322/pnas.2407455121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/4ff16fca740d/pnas.2407455121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/d30adf674365/pnas.2407455121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950a/11406231/adf44652a9a0/pnas.2407455121fig06.jpg

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Nat Commun. 2023 Dec 20;14(1):8480. doi: 10.1038/s41467-023-44245-4.
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Metabolic engineering of Mannheimia succiniciproducens for malic acid production using dimethylsulfoxide as an electron acceptor.利用二甲基亚砜作为电子受体对产琥珀酸黏质沙雷氏菌进行代谢工程改造生产苹果酸。
Biotechnol Bioeng. 2023 Jan;120(1):203-215. doi: 10.1002/bit.28242. Epub 2022 Sep 29.
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Life cycle analysis of fermentative production of succinic acid from bread waste.
面包废弃物发酵生产琥珀酸的生命周期分析。
Waste Manag. 2021 May 1;126:861-871. doi: 10.1016/j.wasman.2021.04.013. Epub 2021 Apr 23.
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Optimized gene expression from bacterial chromosome by high-throughput integration and screening.高通量整合和筛选优化细菌染色体基因表达。
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Intracellular ion concentrations and cation-dependent remodelling of bacterial MreB assemblies.细胞内离子浓度与细菌 MreB 组装体的阳离子依赖性重塑。
Sci Rep. 2020 Jul 20;10(1):12002. doi: 10.1038/s41598-020-68960-w.
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Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase.利用优化的苹果酸脱氢酶提高曼海姆菌琥珀酸的产量。
Nat Commun. 2020 Apr 23;11(1):1970. doi: 10.1038/s41467-020-15839-z.
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