高效定向合成 5-Aminolevulinic Acid 的 Shewanella oneidensis MR-1 模块化工程。

IF 6.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jie Wu , Jing Wu , Ru-Li He , Lan Hu , Dong-Feng Liu , Wen-Wei Li
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引用次数: 0

摘要

Shewanella oneidensis MR-1 在污染物转化和生物能源生产方面有着广泛的应用,这与其出色的血红素合成能力密不可分。然而,这种巨大的生物合成潜力至今仍未得到开发。在这里,我们将这种细菌变成了绿色合成 5-氨基乙酰丙酸(5-ALA)的高效生物工厂,5-ALA 是一种在农业、医药和食品工业中广泛应用的重要化学物质。利用 S. oneidensis 的原生 C5 通路基因,并引入外来抗氧化模块,建立了 5-ALA 生产模块,从而使 5-ALA 产量比广谱型高出 87 倍,耐受性也大幅提高。此外,利用 CRISPR 干扰和碱基编辑技术调节代谢通量,抑制竞争途径,进一步提高了 5-ALA 的滴度。工程菌株的 5-ALA 生产能力是宽型菌株的 123 倍。这项研究不仅为 5-ALA 的生物合成提供了一条极具吸引力的新途径,而且提出了一种多维模块化工程策略,拓宽了 S. oneidensis 的应用范围。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modularized Engineering of Shewanella oneidensis MR-1 for Efficient and Directional Synthesis of 5-Aminolevulinic Acid

Shewanella oneidensis MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in agriculture, medicine, and the food industries. The native C5 pathway genes of S. oneidensis was employed, together with the introduction of foreign anti-oxidation module, to establish the 5-ALA production module, resulting 87-fold higher 5-ALA yield and drastically enhanced tolerance than the wild type. Furthermore, the metabolic flux was regulated by using CRISPR interference and base editing techniques to suppress the competitive pathways to further improve the 5-ALA titer. The engineered strain exhibited 123-fold higher 5-ALA production capability than the wild type. This study not only provides an appealing new route for 5-ALA biosynthesis, but also presents a multi-dimensional modularized engineering strategy to broaden the application scope of S. oneidensis.

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来源期刊
Metabolic engineering
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.
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