工程Saccharomyces cerevisiae用于快速维生素独立的有氧生长
Anja K Ehrmann1, Anna K Wronska2, Thomas Perli2
1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, Building 220, 2800 Kgs, Lyngby, Denmark.
Metabolic engineering
|February 16, 2024
概括
这项研究通过过度表达特定的基因,对Saccharomyces cerevisiae进行了维生素独立生长的工程. 这一成就可以通过降低与维生素补充相关的成本和复杂性来实现更快的工业应用.
科学领域:
- 生物技术是生物技术.
- 微生物生理学 微生物生理学
- 合成生物学 合成生物学
背景情况:
- 培养Saccharomyces cerevisiae通常需要B类维生素以实现最佳生长.
- 缺少维生素会显著降低生长速度,增加工业应用的成本和复杂性.
- 开发维生素独立菌株对于具有成本效益和强大的工业流程至关重要.
研究的目的:
- 为了设计Saccharomyces cerevisiae在没有维生素的介质上生长.
- 识别和过度表达参与维生素生物合成或救援途径的基因.
- 为了实现维生素独立菌株的工业相关增长率.
主要方法:
- 在Saccharomyces cerevisiae的基因工程 CEN.PK113-7D.
- 原生基因 (ScFMS1,ScABZ1/ScABZ2,ScSNZ1/ScSNO1,ScINO1,ScTHI4,ScTHI5) 和异质基因 (Cyberlindnera fabianii BIO1) 的过度表达.
- 在有氧,葡萄糖有限的化学状态条件下,在无维生素的合成介质上进行培养.
- 生理参数分析和转录组分析.
主要成果:
- 过度表达特定的基因在缺少某些维生素的情况下纠正了低于最佳的生长.
- 通过ScTHI4和/或ScTHI5过度表达,实现了胺独立的生长.
- 七个本地基因和CfBIO1的综合过度表达导致0.33 ± 0.01 h-1的最大特异生长率,仅比参考菌株低17%.
- 工程菌株的生理参数和基因表达特征与维生素补充介质中的父菌株相似.
结论:
- 成功开发了维生素独立的Saccharomyces cerevisiae菌株.
- 证明了在没有维生素补充的情况下实现高生长率的可行性.
- 这些发现支持开发具有成本效益和强大的工业酵母菌株.
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