通过转录学和基于约束的建模,对酸诱导的新陈代谢重新连接的机制性见解,以增强S-adenosylmethionine合成
Le Dong1, Weijing Song1, Zhongyue Li1
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People's Republic of China.
Bioprocess and biosystems engineering
|October 13, 2025
概括
酸盐补充剂通过改善能源和前体供应,可以提高Pichia pastoris中的S-adenosylmethionine (SAM) 产量. 这一策略增强了微生物生物合成,用于医学和营养应用.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 微生物生理学 微生物生理学
背景情况:
- S-adenosylmethionine (SAM) 对医学和营养至关重要,但微生物的生产受到能源需求的限制.
- 不高效的前体利用和高能耗要求阻碍了成本有效的SAM生物合成.
研究的目的:
- 调查酸补充剂用于增强Pichia pastoris.中的SAM生产.
- 用omics和建模阐明酸盐介导改善背后的代谢机制.
主要方法:
- 综合转录组学和基因组规模的代谢建模 (iLD1283).
- 在甲醇诱导和酸盐补充下对Pichia pastoris的生理分析.
- 基于约束的模拟和代谢流量分析.
- 料批发发酵的验证. 料批发发酵的验证.
主要成果:
- 酸增加了生物质,甲醇/甲氨酸同化和ATP水平,从而提高了70%的SAM标位.
- 转录学揭示了高调节的中央碳代谢,氧化酸化和氨基酸生物合成.
- 以模型为指导的最佳酸盐料在料批发发酵中达到10.87g/L的SAM.
结论:
- 酸诱导新陈代谢重新连接,改善了SAM生产的能量和前体可用性.
- 一个以模型为导向的框架可以合理优化能源密集型微生物过程.
- 精确养策略与奥米克和建模相结合,可以增强微生物生物生产.
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