Abstract

Microaerobic fermentation has been shown to improve lactose transport and recombinant protein production in Escherichia coli. Mechanistic correlation between lactose and dissolved oxygen has been studied and it has been demonstrated that E. coli can switch its genetic machinery upon fluctuations in dissolved oxygen levels and thereby impact lactose transport, resulting in product formation. Continuous induction of lactose in microaerobic fermentation led to a 3.3-fold improvement in product titre of rLTNF oligomer and a 1.8-fold improvement in product titre of rSymlin oligomer as compared with traditional aerobic fermentation. Transcriptome profiling indicated that ribosome synthesis, lactose transport and amino acid synthesis genes were upregulated during microaerobic fermentation. Besides, novel lactose transporter setB was examined and it was observed that lactose uptake rate was 1.4-fold higher in microaerobic fermentation. The results indicate that microaerobic fermentation can offer a superior alternative for industrial production of recombinant therapeutics, industrial enzymes and metabolites in E. coli.

Key points

• Microaerobic fermentation results in significantly improved protein production

• Lactose transport, ribosome synthesis and amino acid synthesis are enhanced

• Product titre improves by 1.8–3.3-fold

中文翻译：

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微有氧发酵会改变大肠杆菌中的乳糖代谢。

摘要

微有氧发酵可以改善大肠杆菌中的乳糖运输和重组蛋白的生产。研究了乳糖和溶解氧之间的机制相关性，并证明大肠杆菌可以在溶解氧水平波动时改变其遗传机制，从而影响乳糖运输，从而导致产物形成。与传统的有氧发酵相比，在微需氧发酵中连续诱导乳糖导致rLTNF低聚物的产物滴度提高了3.3倍，rSymlin低聚物的产物滴度提高了1.8倍。转录组分析表明，核糖体合成，乳糖转运和氨基酸合成基因在有氧发酵过程中被上调。此外，新型乳糖转运蛋白setB进行了检查，结果发现在有氧发酵中乳糖的摄取率高了1.4倍。结果表明，微需氧发酵可以为大肠杆菌中重组治疗剂，工业酶和代谢产物的工业生产提供更好的选择。

关键点

•有氧发酵可显着提高蛋白质产量

•增强乳糖运输，核糖体合成和氨基酸合成

•产品滴度提高了1.8–3.3倍