细菌细菌的组合代谢工程使其能够有效地从奎尔丁中生物合成异基素
Tengfei Niu1,2, Chaokang Huang1, Rufeng Wang3,4,5
1Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Microbial cell factories
|April 19, 2024
概括
这项研究工程 Bacillus subtilis 产生异quercitrin,一个有价值的治疗化合物. 优化的微生物生物转化实现了创纪录的35.6g/L的异quercitrin,为工业规模生产铺平了道路.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
背景情况:
- 易索克尔,一种类甘油酸,显示治疗潜力,但由于有限的自然丰度和复杂的合成,面临生产挑战.
- 微生物生物转化为异quercitrin生产提供了一个可持续的替代方案,但目前的产量不足以用于工业应用.
研究的目的:
- 通过代谢工程来设计Bacillus subtilis,以通过代谢工程来生产高水平的异quercitrin.
- 优化微生物细胞工厂,以有效地将奎尔素转化为异奎尔素.
主要方法:
- 在 Bacillus subtilis 中,UGT78D2 葡萄糖转移酶基因的异质表达.
- 重建UDP-葡萄糖合成途径,并破坏竞争的代谢途径 (奎尔酸代谢和异奎尔酸水解).
- 通过破坏pgi基因来增强细胞内UDP-葡萄糖池.
主要成果:
- 在基因表达和途径重建后,获得了0.37-0.42g/L的初始异基氨酸标位.
- 通过阻断奎尔氨酸降解,提升标位至1.64g/L,通过消除异奎尔氨酸水解,提升至3.58g/L.
- 通过在发酵器中增加UDP-葡萄糖池,达到35.6g/L的最大标位,对奎尔素产生77.2%的产量.
结论:
- 改造后的Bacillus subtilis菌株显示出可持续大规模工业化生产异基的巨大潜力.
- 开发的策略为增强使用微生物细胞工厂生产其他黄类甘氨酸的生产提供了宝贵的参考.
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