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通过模块化路径优化在工程 Bacillus subtilis 中进行工业规模的 Lacto-N-tetraose 生产

Chunhua Wang¹, Shaoru Hu¹, Shenglong Wang¹

¹Key Laboratory of Industrial·Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, China.

Metabolic engineering

|October 31, 2025

概括

细菌细菌被改造为产生乳酸-N-四糖 (LNT),这是一个益生菌人乳寡糖化物. 这种GRAS生物体实现了创纪录的80.48g/L产量,证明了其对婴儿营养的潜力.

科学领域:

生物技术是生物技术.
代谢工程是代谢工程.
微生物发酵微生物发酵

背景情况:

乳酸-N-四糖 (LNT) 是一种具有显著益生菌性质的关键人乳寡糖.
开发有效的微生物平台用于LNT生产对于婴儿营养成分至关重要.

研究的目的:

建立Bacillus subtilis作为GRAS (一般公认的安全) 平台,用于新的LNT生物合成.
通过先进的代谢工程和精确的监管策略,实现高位数LNT生产.

主要方法:

酶查确定了用于LNT合成的关键酶:β-1,3-银酸转移酶,β-1,3-N-乙糖氨基转移酶和β-银酸透酶 (LacY).
代谢工程策略包括途径优化,破坏竞争途径和增强前体流.
一个CRISPR干扰 (CRISPRi) 系统被开发来降低基本的竞争基因,优化碳流.

主要成果:

改造的BPPY菌株取得了1.42g/L的初始LNT产量.
通过先进的代谢工程,BPPY31菌株通过先进的代谢工程达到7.83g/L LNT.
菌株BD7在料批生物反应器中产生了创纪录的80.48 g/L LNT,其基质转化率高,副产品形成最小.

结论:

细菌细菌 (Bacillus subtilis) 作为一个可行的和可扩展的GRAS平台用于工业LNT生产.
这项研究实现了迄今为止报告的最高LNT标位,展示了精确的代谢调节和生物制造潜力.
开发的微生物平台对低成本生产婴儿营养母乳寡糖糖具有显著的前景.

关键词:

这种细菌是 Bacillus subtilis.克里斯普里是指克里斯普里.乳酸-N-四糖是一种乳糖.路径工程工程的路径工程.

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