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高效琥珀酰高丝氨酸生产细胞工厂的构建及其在耦合生产甲硫氨酸和琥珀酸中的应用。

Construction of an Efficient -Succinyl--homoserine Producing Cell Factory and Its Application for Coupling Production of -Methionine and Succinic Acid.

作者信息

Tang Xiao-Ling, Liu Yan-Lai, Zhao Kang, Li Rui, Chen Jing-Xiang, Liu Zhi-Qiang, Zheng Yu-Guo

机构信息

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

出版信息

J Agric Food Chem. 2025 Jan 22;73(3):2068-2076. doi: 10.1021/acs.jafc.4c10092. Epub 2025 Jan 7.

Abstract

-Succinyl--homoserine (OSH) is an important C4 platform compound with broad applications. Its green and efficient production is receiving increasing attention. Herein, the OSH producing chassic cell was constructed by deleting the transcriptional negative regulation factor, blocking the OSH consumption pathway, and inhibiting the competitive bypass pathways. The precursor synthesis pathways of aspartic acid and homoserine were further strengthened, and the pentose phosphate pathway and glycolysis pathway were modified to enhance the NADPH supply. Adaptive evolution was applied to improve the tolerance of the cell factory to the fermentation environment. With Raman online analysis, the metabolic process model was built to guide fermentation regulation. The final titer of OSH reached 121.7 g/L with conversion of 63% in a 50 L fermenter. Based on this, a coupling production route for -methionine and succinic acid from OSH was established with good atomic economy and environmental friendliness.

摘要

琥珀酰高丝氨酸(OSH)是一种具有广泛应用的重要C4平台化合物。其绿色高效生产受到越来越多的关注。在此,通过删除转录负调控因子、阻断OSH消耗途径和抑制竞争性旁路途径构建了生产OSH的底盘细胞。进一步强化了天冬氨酸和高丝氨酸的前体合成途径,并对磷酸戊糖途径和糖酵解途径进行了改造以增强NADPH供应。应用适应性进化来提高细胞工厂对发酵环境的耐受性。通过拉曼在线分析,建立了代谢过程模型以指导发酵调控。在50 L发酵罐中,OSH的最终产量达到121.7 g/L,转化率为63%。在此基础上,建立了一条从OSH联产甲硫氨酸和琥珀酸的路线,具有良好的原子经济性和环境友好性。

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