全细胞生物合成的分支人类牛奶 六糖酸乳酸-N-neohexaose
Yinshuang Li1,2, Yi Li1, Pengfei Li1
1National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, Shandong 266237, China.
Journal of agricultural and food chemistry
|July 2, 2025
概括
研究人员对大肠杆菌进行了改造,使其产生乳酸-N-新糖 (LNnH),这是一种关键的分支人乳寡糖化物 (HMO). 这一突破使得可扩展的生产各种各样的分支HMO用于各种应用.
科学领域:
- 生物技术是生物技术.
- 葡萄糖科学 (Glycoscience) 是一种科学.
- 代谢工程是代谢工程.
背景情况:
- 分支母乳寡糖化物 (HMO) 对婴儿健康至关重要,但很难生产.
- 用于β-1,6-GlcNAc分支的酶 (GCNT2) 无法获得,限制了分支的HMO合成.
- 工程微生物菌株是需要高效和可扩展的生产复杂的HMO结构.
研究的目的:
- 开发一种代谢工程 *Escherichia coli* 菌株,用于全细胞合成乳酸-N-新糖 (LNnH).
- 通过生产LNnH,基础结构,使各种各样的分支HMO可访问.
- 为生产有价值的分支HMO建立一个强大的平台.
主要方法:
- 对于β-1,6-GlcNAc分支而言,大肠杆菌的代谢工程.
- 实现了人类β-1,6-N-乙糖氨基转移酶2 (GCNT2) 的可溶性表达.
- 优化了LNnH生物合成途径,并在生物反应堆中扩大了生产规模.
主要成果:
- 成功设计了*大肠杆菌*用于全细胞LNnH合成.
- 在工程菌株中,LNnH产量从1.04增加到21.19 mg/L.
- 在5L生物反应器中达到173.21mg/L的最终LNnH产量,增加了166.5倍.
结论:
- 开发的全细胞生物合成策略为生产分支HMO提供了强大的方法.
- 这种方法克服了分支HMO生产中酶难以获得的局限性.
- 这项研究推进了HMO glycomics,并为分支HMO的生物应用开辟了新的可能性.
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