益生菌Saccharomyces boulardii的多步路径工程,用于肠道中酸的产生
Femke Van Gaever1,2, Paul Vandecruys3,4, Yasmine Driege1,2
1VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium.
Metabolic engineering communications
|June 18, 2025
概括
工程化益生菌酵母Saccharomyces boulardii在肠道中产生酸 (ABA). 虽然在肠道中成功,但低体温阻碍了ABA的产生,需要进一步优化治疗用途.
科学领域:
- 微生物学 微生物学
- 植物科学 植物科学
- 生物技术是生物技术.
背景情况:
- 由于其免疫和抗炎作用,酸 (ABA) 作为营养药物表现有前途.
- 目前的ABA交付方法在可扩展性,稳定性和成本方面存在局限性.
- 开发新的ABA输送系统对于其治疗应用至关重要.
研究的目的:
- 为了设计一种益生菌酵母,Saccharomyces boulardii,用于现场生产和在肠道中输送酸 (ABA).
- 为了克服与ABA短半衰期和成本效益生产相关的挑战.
- 在生理温度下研究工程S. boulardii的ABA生产.
主要方法:
- 用S. boulardii的基因工程与Botrytis cinerea的基因用于ABA生物合成.
- 通过引入细胞染色体P450减少酶基因来优化ABA生产.
- 在体内向小鼠注射工程S. boulardii,并评估肠道殖民和血清ABA水平.
- 研究生理温度 (37°C) 对ABA产生的影响.
主要成果:
- 工程S. boulardii成功地在30°C下产生了ABA,其标位明显高于之前报告的S. cerevisiae菌株.
- 益生菌在食补充剂后有效地殖民了小鼠肠道.
- 在生理老鼠体温 (37°C) 时,ABA产量显著降低,导致血清ABA水平较低.
- 对美瓦酸路径的改进显示,在37°C时有可能改善ABA产量.
结论:
- 工程设计的S. boulardii可以在肠道中产生ABA,但生理温度是有效生产的主要限制.
- 需要进一步的代谢工程来优化37°C的ABA产量,然后才能探索治疗应用.
- 这项研究为益生菌介导的ABA输送提供了一个有希望的平台,等待进一步优化.
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