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在酵母 Komagataella phaffii 酵母中的工程氧化酶代谢
Kun Zhang1, Xin Ni2, Peng Cai3
1Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China; Henan Engineering Laboratory for Bioconversion Technology of Functional Microbes, College of Life Sciences, Henan Normal University, Xinxiang 453007, Henan, PR China.
Metabolic engineering
|February 8, 2026
概括
这项研究通过引入新的代谢途径和阻止其他代谢途径来设计Komagataella phaffii以有效利用氧化糖. 适应性实验室进化显著提高了酸盐消耗和生物质产量,为改进的酵母生物加工铺平了道路.
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:
- 有效利用纤维糖,是细胞生物质的主要组成部分,对于具有成本效益的生物燃料和生物化学品生产至关重要.
- Komagataella phaffii是一种工业相关的酵母,但表现出较差的原生纤维素同化能力,限制了其在生物质价值化中的应用.
研究的目的:
- 为了改造K. phaffii以增强其生长和新陈代谢,它将使用西洛斯作为唯一的碳来源.
- 为了识别和克服K. phaffii.内部的氧化糖代谢中的瓶.
- 为了提高K. phaffii的整体代谢可塑性,以便更广泛地利用基质.
主要方法:
- 构建关键的西洛斯同化路径:西洛斯异构酶 (XI) -西洛基因酶 (XK),非氧化酸路径 (PPP) 和非氧化糖解 (NOG).
- 代谢工程策略包括阻断旁路 (例如,HOG-MAPK信号) 和抑制负转录因子.
- 适应性实验室进化 (ALE) 的应用与多组学和逆向工程相结合,以优化西洛斯的利用.
主要成果:
- 改造后的K. phaffii菌株在克西洛斯上实现了报告中最高的特定生长率 (μmax = 0.042 h-1).
- 证明了显著的生物质产量 (0.366g DCW/g xylose) 和减少的滞后时间 (25.0小时) 在最小的介质上生长期间,用.
- 观察到加速的代谢物循环,有效的自由脂肪酸 (FFA) 生产,以及部分缓解葡萄糖抑制效应.
结论:
- 通过整合代谢途径的构建和优化,成功设计了K. phaffii以进行强大的二氧化糖同化.
- 开发的菌株在树脂糖利用方面表现出卓越的性能,为生物质价值化提供了一个有前途的平台.
- 代谢工程策略和所获得的见解可转移到其他酵母物种,以增强它们的西洛斯代谢能力.
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