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 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 .

中文翻译：

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Shewanella oneidensis MR-1的模块化工程用于高效定向合成5-氨基乙酰丙酸


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切相关。然而，这种重要的生物合成潜力迄今为止仍未得到开发。在这里，我们将这种细菌转变为高效生物工厂，用于绿色合成 5-氨基乙酰丙酸 (5-ALA)，这是一种在农业、医药和食品工业中广泛应用的重要化学品。利用天然C5途径基因，并引入外源抗氧化模块，建立5-ALA生产模块，使5-ALA产量比野生型高87倍，耐受性大幅增强。此外，通过使用CRISPR干扰和碱基编辑技术来调节代谢通量，抑制竞争途径，进一步提高5-ALA滴度。工程菌株的 5-ALA 生产能力比野生型高 123 倍。该研究不仅为5-ALA生物合成提供了一条有吸引力的新路线，而且提出了多维模块化工程策略，以拓宽5-ALA的应用范围。