基于代谢组学分析的O-琥珀酰-L-高丝氨酸发酵调控  

Regulation of fermentation for O-succinyl-L-homoserine production based on metabolomics

作　　者：陈晨 刘彦来 陶方稳 汤晓玲 柳志强 CHEN Chen;LIU Yanlai;TAO Fangwen;TANG Xiaoling;LIU Zhiqiang(College of Biotechnology and Bioengineering,Zhejiang University of Technology,Hangzhou 310014,Zhejiang,China)

机构地区：[1]浙江工业大学生物工程学院,浙江杭州310014

出　　处：《微生物学报》2023年第12期4783-4799,共17页Acta Microbiologica Sinica

基　　金：国家重点研发计划(2018YFA0901400)。

摘　　要：【目的】O-琥珀酰-L-高丝氨酸(O-succinyl-L-homoserine,OSH)是合成L-蛋氨酸、L-草铵膦等重要前体,在医药、农药、食品等领域具有重要的应用前景,其绿色高效制造受到广泛关注。本研究通过解析OSH发酵过程代谢途径和代谢产物变化规律,建立OSH发酵调控策略,提升其产量和糖酸转化率。【方法】运用代谢组学技术,系统考察OSH生产菌在发酵不同时间段的代谢物变化情况,探究与OSH合成显著关联的代谢途径,通过在不同时间外源添加关键代谢物,平衡关键代谢物及其前体通量,减少旁路途径对前体的竞争性利用。【结果】在5 L发酵罐中产量达70.1 g/L,糖酸转化率达0.52 g/g(葡萄糖)。【结论】研究结果表明,基于代谢组学分析技术的OSH发酵体系优化和发酵过程调控显著提升了目标产物生产效率,奠定了OSH的产业化基础。[Objective]O-Succinyl-L-homoserine(OSH),an important precursor for the synthesis of L-methionine,L-glufosinate-ammonium and other chemicals,has wide applications in the pharmaceutical,pesticide,and food industries.The green and efficient production of OSH has attracted a great deal of attention.This study investigated the metabolic pathway and metabolite changes during the microbial fermentation for production of OSH,aiming to establish an efficient regulation strategy to increase both the yield and sugar-acid conversion of OSH.[Methods]Metabolomics was employed to systematically investigate the metabolic changes during the fermentation,and the key metabolic pathways associated with OSH biosynthesis were determined.The key metabolites were added at different fermentation stages to balance the metabolic flux and reduce the competitive utilization of precursors.[Results]The efficient bio-production of OSH was realized in a 5 L fermentation tank.The titer reached 70.1 g/L with the conversion of 0.52 g/g(glucose).[Conclusion]The optimization of OSH fermentation system and regulation of fermentation process based on metabolomics have significantly improved the production of OSH,laying a foundation for the industrialization of OSH.

关 键 词：代谢组学 O-琥珀酰-L-高丝氨酸 细胞工厂 发酵调控 

分 类 号：TQ922[轻工技术与工程—发酵工程]