Ectoine hyperproduction by engineered Halomonas bluephagenesis

IF 6.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Qitiao Hu , Simian Sun , Zhongnan Zhang , Wei Liu , Xueqing Yi , Hongtao He , Nigel S. Scrutton , Guo-Qiang Chen
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引用次数: 0

Abstract

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 Halomonas bluephagenesis for ectoine production by overexpressing ectABC operon, increasing precursors availability, enhancing product transport system and optimizing its growth medium. The final engineered H. bluephagenesis 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-co-4HB) by the engineered H. bluephagenesis. The unsterile fermentation process and significantly increased ectoine titer indicate that H. bluephagenesis 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.

工程化蓝光单胞菌的外氨酸超量生产
辛胺是嗜盐生物适应盐分的一种重要渗透保护剂,在化妆品和医疗行业受到越来越多的关注。然而,模型微生物严格的发酵过程和原生生产者较低的生产水平使其生产仍面临挑战。在这里,我们通过过表达 ectABC 操作子、增加前体可用性、增强产物运输系统和优化生长介质,系统地改造了原生的埃克妥因生产者 Halomonas bluephagenesis 来生产埃克妥因。在没有质粒、抗生素或诱导剂的情况下,在 7 升生物反应器中开放式无菌培养 52 小时后,最终设计的 H. bluephagenesis 可生产 85 克/升的埃克托碱。此外,研究还成功证明了盐浓度与外藤氨酸合成脱钩的可行性,并证明了工程化 H. bluephagenesis 与生物塑料 P(3HB-co-4HB)联合生产的可行性。非无菌发酵过程和明显增加的外藤氨酸滴度表明,作为下一代工业生物技术(NGIB)的底盘,H. bluephagenesis 在细胞内生物塑料 PHA 和小分子化合物(如外藤氨酸)的生物制造方面前景广阔。
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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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