脂肪酸原料可实现高效乙醛酸-TCA 循环,从而高产生产 β-丙氨酸。

IF 3.5 1区 环境科学与生态学 Q1 ECOLOGY
Journal of Animal Ecology Pub Date : 2022-06-19 eCollection Date: 2022-06-01 DOI:10.1002/mlf2.12006
Yingchun Miao, Jiao Liu, Xuanlin Wang, Bo Liu, Weifeng Liu, Yong Tao
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引用次数: 0

摘要

生产三羧酸(TCA)循环衍生化学物质的代谢工程通常存在产量低和细胞代谢受损的问题。在这项工作中,我们发现脂肪酸(FA)原料可以高产生产 TCA 循环衍生化学品,同时保持乙醛酸-TCA 循环高效、平衡的代谢通量,这对产品合成和细胞生长都有利。在此,我们设计了一种新的合成途径,可从 FAs 中生产出重要的 TCA 循环衍生产物--β-丙氨酸,其理论产量高达 1.391 克/克。通过引入 panD、改进 aspA 和敲除 iclR,乙醛酸分流在脂肪酸中被高度激活,来自脂肪酸的 β-丙氨酸产量达到 0.71 g/g,远高于来自葡萄糖的产量。在icd/sucA/fumAC节点阻断TCA循环可提高烧瓶培养中的β-丙氨酸产量,但在分批喂养过程中会严重降低细胞生长和FA利用率。通过敲除 aspC 和恢复 fumAC 来补充草酰乙酸,可以恢复生长并使滴度达到 35.57 克/升。在缓解了 FA 代谢引起的氧化应激后,β-丙氨酸产量可达 72.05 克/升,最高产量为 1.24 克/克,约为理论产量的 86%。因此,我们的研究为生产 TCA 循环衍生化学品提供了一种前景广阔的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fatty acid feedstocks enable a highly efficient glyoxylate-TCA cycle for high-yield production of β-alanine.

Metabolic engineering to produce tricarboxylic acid (TCA) cycle-derived chemicals is usually associated with problems of low production yield and impaired cellular metabolism. In this work, we found that fatty acid (FA) feedstocks could enable high-yield production of TCA cycle-derived chemicals, while maintaining an efficient and balanced metabolic flux of the glyoxylate-TCA cycle, which is favorable for both product synthesis and cell growth. Here, we designed a novel synthetic pathway for production of β-alanine, an important TCA cycle-derived product, from FAs with a high theortecial yield of 1.391 g/g. By introducing panD, improving aspA, and knocking out iclR, glyoxylate shunt was highly activated in FAs and the yield of β-alanine reached 0.71 g/g from FAs, much higher than from glucose. Blocking the TCA cycle at icd/sucA/fumAC nodes could increase β-alanine yield in a flask cultivation, but severely reduced cell growth and FA utilization during fed-batch processes. Replenishing oxaloacetate by knocking out aspC and recovering fumAC could restore the growth and lead to a titer of 35.57 g/l. After relieving the oxidative stress caused by FA metabolism, β-alanine production could reach 72.05 g/l with a maximum yield of 1.24 g/g, about 86% of the theoretical yield. Our study thus provides a promising strategy for the production of TCA cycle-derived chemicals.

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来源期刊
Journal of Animal Ecology
Journal of Animal Ecology 环境科学-动物学
CiteScore
9.10
自引率
4.20%
发文量
188
审稿时长
3 months
期刊介绍: Journal of Animal Ecology publishes the best original research on all aspects of animal ecology, ranging from the molecular to the ecosystem level. These may be field, laboratory and theoretical studies utilising terrestrial, freshwater or marine systems.
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