ATP 代谢的协调重编程可大大提高大肠杆菌的己二酸产量。

IF 6.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Metabolic engineering Pub Date : 2024-10-23 DOI:10.1016/j.ymben.2024.10.010

Soo Young Moon , Nan Yeong An , Seung Soo Oh , Ju Young Lee

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引用次数: 0

摘要

保持腺苷-5'-三磷酸（ATP）的微妙平衡不仅对优化细胞功能至关重要，而且对提高代谢产物的产量也至关重要，这表明在代谢工程中需要仔细调节 ATP 需求。本研究以反向己二酸降解途径（RADP）为重点，探索了如何改变 ATP 代谢以提高大肠杆菌的己二酸产量，并通过控制基因（panK 和 acs）的过量表达对 ATP 消耗循环进行了微调，以平衡 ATP 消耗和己二酸产量。结果，与对照菌株（携带 RADP 的野生型大肠杆菌）相比，我们成功地使己二酸产量大幅增加（19.5 倍），在摇瓶中达到 1,093.11 mg/L。我们的转录组分析表明，调节 ATP 代谢以及途径前体的平衡供应会影响代谢通量，从而增强大肠杆菌的己二酸生物合成。这项研究表明，ATP 的代谢重编程有可能满足生物合成的需求，从而提高己二酸和其他 ATP 衍生化学物质的产量。

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Coordinated reprogramming of ATP metabolism strongly enhances adipic acid production in Escherichia coli

Maintaining a delicate balance of adenosine-5′-triphosphate (ATP) is crucial not only for optimal cellular functions but also for improved metabolite production, indicating the need for careful regulation of ATP demands in metabolic engineering. This study explored the modification of ATP metabolism to enhance adipic acid production in Escherichia coli, focusing on the reverse adipate degradation pathway (RADP), and ATP-consuming cycles were fine-tuned by controlling the overexpression of genes (panK and acs) to balance ATP consumption and adipic acid production. As a result, we successfully achieved a significant increase (19.5-fold) in adipic acid production, reaching 1093.11 mg/L in a shake flask, compared to that in the control strain (wild-type E. coli harboring the RADP). Our transcriptomic analysis indicated that modulation of ATP metabolism, along with a balanced supply of pathway precursors, affects metabolic fluxes, enhancing adipic acid biosynthesis in E. coli. This study suggests the potential of metabolic reprogramming of ATP to meet biosynthetic demands, which may improve the production of adipic acid and other ATP-derived chemicals.

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来源期刊

Metabolic engineering 工程技术-生物工程与应用微生物

CiteScore

15.60

自引率

6.00%

发文量

140

审稿时长

44 days

期刊介绍： Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.