通过2A基平台进行模块化代谢工程,以改善阿拉基酸生产
Huidan Zhang1,2,3, Weijian Wan1,2,3, Qiu Cui1,2,3
1CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101, China.
Journal of agricultural and food chemistry
|August 10, 2023
概括
研究人员设计了一种真菌,以产生一种必需脂肪酸 - - 阿拉基酸 (ARA). 这种模块化方法通过优化代谢途径显著提高了ARA产量,在发酵过程中达到4.4 g/L的标位.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 工业微生物学 工业微生物学
背景情况:
- 阿拉基酸 (ARA) 是一种对人类健康至关重要的omega-6脂肪酸.
- 丝状真菌是ARA生产的成熟平台.
- 代谢途径的瓶限制了微生物宿主中有效的ARB生物合成.
研究的目的:
- 为了增强丝状真菌中的阿拉基酸 (ARA) 生产.
- 为了克服ARA延长酶/脱酶通路中的代谢限制.
- 开发一个模块化工程策略,以提高微生物代谢物产量.
主要方法:
- 将ARA延长酶/脱酶路径重塑为功能性的"推"和"拉"模块.
- 使用基于2A的平台,以实现高效的多基因多基因表达.
- 模块的组合优化,以平衡中间代谢物流量.
主要成果:
- 改造的MA5菌株显示,总脂质含量增加了1.2倍.
- 工程菌株中的ARA含量增加了77.6%.
- 实现了ARA产量的五倍增加,在摇瓶发酵中达到4.4g/L的最终标位.
结论:
- 模块化工程有效地解决了ARA生产中的代谢瓶.
- 开发的战略为工程细胞工厂提供了一个通用的方法.
- 在ARA产量的显著改善表明了工业规模生物合成的潜力.
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