Ectoine, a crucial osmoprotectant for salt adaptation in halophiles, has gained growing interest in cosmetics and medical industries. However, its production remains challenged by stringent fermentation process in model microorganisms and low production level in its native producers. Here, we systematically engineered the native ectoine producer for ectoine production by overexpressing operon, increasing precursors availability, enhancing product transport system and optimizing its growth medium. The final engineered produced 85 g/L ectoine in 52 h under open unsterile incubation in a 7 L bioreactor in the absence of plasmid, antibiotic or inducer. Furthermore, it was successfully demonstrated the feasibility of decoupling salt concentration with ectoine synthesis and co-production with bioplastic P(3HB--4HB) by the engineered . The unsterile fermentation process and significantly increased ectoine titer indicate that as the chassis of Next-Generation Industrial Biotechnology (NGIB), is promising for the biomanufacturing of not only intracellular bioplastic PHA but also small molecular compound such as ectoine.

中文翻译：

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通过工程化的蓝色盐单胞菌过量生产四氢嘧啶

四氢嘧啶是嗜盐生物盐适应的重要渗透保护剂，在化妆品和医疗行业中越来越受到关注。然而，其生产仍然受到模型微生物严格发酵过程和本土生产者生产水平低的挑战。在这里，我们通过过度表达操纵子、增加前体可用性、增强产品运输系统和优化其生长培养基，系统地改造了用于四氢嘧啶生产的天然四氢嘧啶生产者。最终的工程在 7 L 生物反应器中，在没有质粒、抗生素或诱导剂的情况下，在开放式未灭菌培养下，在 52 小时内产生了 85 g/L 四氢嘧啶。此外，还成功证明了通过工程设计将盐浓度与四氢嘧啶合成解耦以及与生物塑料P(3HB--4HB)联产的可行性。未灭菌的发酵过程和显着增加的四氢嘧啶滴度表明，作为下一代工业生物技术（NGIB）的基础，不仅可以用于细胞内生物塑料PHA的生物制造，还可以用于四氢嘧啶等小分子化合物的生物制造。