基因组缩小改善了在缩小生物反应器中的八酸生产
William T Cordell1, Gennaro Avolio2, Ralf Takors2
1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Microbial biotechnology
|November 7, 2024
概括
工程化大肠杆菌菌株WG02,一种代谢优化的菌株,通过减轻营养梯度的压力反应,增强生物质和生物反应器中的八酸生产. 这降低了生物工艺扩展的风险.
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:
- 微生物生物反应器因混合限制而面临异质条件的挑战.
- 大规模培养中的营养梯度可以触发浪费的压力反应,降低生物过程效率.
- 生物工艺的扩展带有重大风险,因为环境异质性的不可预测影响.
研究的目的:
- 设计一种代谢优化的大肠杆菌菌株 (WG02),用于从糖醇中增强酸生产.
- 在各种生物反应器条件下,与标准大肠杆菌菌株 (WG01) 相比,评估WG02的性能.
- 评估工程代谢成本降低对生物工艺扩展的影响.
主要方法:
- 通过降低基因组代谢负荷,改造了大肠杆菌菌株RM214 (WG02).
- 对比WG02和E. coli MG1655 (WG01) 在批量瓶和料批量生物反应器培养中.
- 使用碳限制,限制和缩小规模 (动+插头流反应堆) 的生物反应器系统.
主要成果:
- 在碳限量养批次中,WG02与WG01相比,WG02增加了超过22%的生物质,具有相似的八酸度.
- 通过减少生物质积累,WG02的有限的种植产生了16%的高氧化酸 titre.
- 在一个缩小系统中,WG02提高了近18%的八度酸位数,同时保持了可比生物质.
结论:
- 代谢优化的大肠杆菌菌株可以减轻生物反应器中间歇性压力的负面影响.
- 降低平台菌株的基因组代谢成本,可以在扩展过程中提高生物工艺性能.
- 在具有挑战性的生物反应器环境中,WG02证明了氧酸合成的强度和生产率的提高.
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