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从甲醇中增强生产3-基酸 (3-HP) 的Komagataella phaffii的代谢工程

Sílvia Àvila-Cabré¹, Joan Albiol¹, Pau Ferrer²

¹Department of Chemical, Biological and Environmental Engineering, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Catalonia, Spain.

Journal of biological engineering

|February 20, 2025

概括

通过优化前体供应和利用乳酸转运物来提高出口效率,Komagataella phaffii酵母的代谢工程增强了3-基酸 (3-HP) 生产. 这导致3HP标位和生产率从甲醇显著更高.

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:

甲醇生物转化为增值化学品,为化石燃料提供了一个可持续的替代方案.
3-基酸 (3-HP) 是一个关键的生物基化学构建块.
目前在Komagataella phaffii中生产的3-HP面临着标位,产量和生产率的限制.

研究的目的:

为了增强Komagataella phaffii.中的3-基酸 (3-HP) 生产.
为了改善前体供应,并将碳流转向3HP合成.
优化3HP出口机制以提高效率.

主要方法:

使用了组合代谢工程策略.
参与前体供应的基因过度表达 (例如,PYC2).
过度表达单碳酸盐载体 (例如,ESBP6,JEN1) 进行增强的3HP出口.

主要成果:

PYC2过度表达显著增加了生物质上的3HP产量.
对PYC2,ESBP6和JEN1的联合过度表达使3-HP标位提高了55%,产量也提高了.
工程菌株实现了27.0 g/L 3-HP,在料批培养中产量为0.19 g/g,生产率为0.56 g/L/h.
过度表达单碳酸盐转运体在低pH下增强了应变强度.

结论:

乳酸运输体 (ESBP6,JEN1) 在K. phaffii.中对3-HP出口有效.
代谢工程策略可以显著提高从甲醇的3HP产量.
优化的菌株显示出工业规模生物化学制造的潜力.

关键词:

科玛格塔贝拉 (Komagataella phaffii) 是一个有趣的植物.这就是Pichia pastoris.3 - 基烯酸是3 - 基烯酸中的一种乳酸运输体是一种乳酸运输体.代谢工程是代谢工程.甲醇是甲醇中的一种.在β-氨酸通路上.

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