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Escherichia coli minicells with targeted enzymes as bioreactors for producing toxic compounds
Metabolic Engineering ( IF 8.4 ) Pub Date : 2022-08-12 , DOI: 10.1016/j.ymben.2022.08.006
Seung-Jin Kim 1 , Woojin Chang 1 , Min-Kyu Oh 1
Affiliation  

Formed by aberrant cell division, minicells possess functional metabolism despite their inability to grow and divide. Minicells exhibit not only superior stability when compared with bacterial cells but also exceptional tolerance—characteristics that are essential for a de novo bioreactor platform. Accordingly, we engineered minicells to accumulate protein, ensuring sufficient production capability. When tested with chemicals regarded as toxic against cells, the engineered minicells produced titers of C6–C10 alcohols and esters, far surpassing the corresponding production from bacterial cells. Additionally, microbial autoinducer production that is limited in expanding bacterial population was conducted in the minicells. Because bacterial population growth was nonexistent, the minicells produced autoinducers in constant amounts, which allowed precise control of the bacterial population having autoinducer-responsive gene circuits. When bacterial population growth was nonexistent, the minicells produced autoinducers in constant amounts, which allowed precise control of the bacterial population having autoinducer-based gene circuits with the minicells. This study demonstrates the potential of minicells as bioreactors suitable for products with known limitations in microbial production, thus providing new possibilities for bioreactor engineering.



中文翻译:

带有靶向酶的大肠杆菌微细胞作为生产有毒化合物的生物反应器

由异常细胞分裂形成的小细胞尽管无法生长和分裂,但仍具有功能代谢。与细菌细胞相比,小细胞不仅表现出卓越的稳定性,而且表现出卓越的耐受性——这些特征对于从头开始至关重要生物反应器平台。因此,我们设计了小细胞来积累蛋白质,确保足够的生产能力。当用被认为对细胞有毒的化学物质进行测试时,工程化的小细胞产生了 C6-C10 醇和酯的滴度,远远超过了细菌细胞的相应产量。此外,在微细胞中进行了微生物自诱导剂的产生,其在扩大细菌种群方面受到限制。由于不存在细菌种群生长,因此小细胞以恒定量产生自诱导物,从而可以精确控制具有自诱导物响应基因回路的细菌种群。当细菌种群不存在时,小细胞会产生恒定数量的自诱导物,这允许精确控制具有基于自诱导基因的基因回路与小细胞的细菌群。这项研究证明了微细胞作为生物反应器的潜力,适用于微生物生产中已知限制的产品,从而为生物反应器工程提供了新的可能性。

更新日期:2022-08-17
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