通过碳和氧化还原再平衡,工程解脂耶氏菌生产β-胡萝卜素。

IF 5.7 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Journal of Biological Engineering Pub Date : 2025-01-15 DOI:10.1186/s13036-025-00476-1
Hojun Lee, Jinwoo Song, Sang Woo Seo
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引用次数: 0

摘要

背景:β-胡萝卜素是一种天然产物,已经获得了显著的商业利益。通过微生物的代谢工程已经做出了相当大的努力来满足这一需求,但仍有改进的潜力。在这项研究中,包括碳和氧化还原再平衡在内的工程方法被用于最大限度地提高脂耶氏菌的β-胡萝卜素产量。结果:通过反复过表达途径基因,去除番茄红素抑制,提高了初始生产水平。为了进一步改进,研究人员评估了两种重新定向中心碳途径的方法,以增加NADPH再生并减少ATP消耗。通过戊糖磷酸途径推动通量和引入NADP+依赖的甘油醛-3-磷酸脱氢酶比磷酸酮酶-磷酸转乙酰酶(PK-PTA)途径更有效。此外,脂质生物合成途径的通量适度增加,以更好地适应增加的β-胡萝卜素库,导致产量水平为809.2 mg/L。结论:通过多途径迭代过表达、中心碳途径工程和脂质途径通量调节,成功构建了基于Y. lipolytic的β-胡萝卜素生产底盘。本文提出的方法为未来提高微生物萜类化合物生产能力的努力提供了见解。
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Engineering Yarrowia lipolytica for the production of β-carotene by carbon and redox rebalancing.

Background: β-Carotene is a natural product that has garnered significant commercial interest. Considerable efforts have been made to meet such demand through the metabolic engineering of microorganisms, yet there is still potential for improvement. In this study, engineering approaches including carbon and redox rebalancing were used to maximize β-carotene production in Yarrowia lipolytica.

Results: The initial production level was increased by iterative overexpression of pathway genes with lycopene inhibition removal. For further improvement, two approaches that redirect the central carbon pathway were evaluated to increase NADPH regeneration and reduce ATP expenditure. Pushing flux through the pentose phosphate pathway and introducing NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase were found to be more effective than the phosphoketolase-phosphotransacetylase (PK-PTA) pathway. Furthermore, flux to the lipid biosynthesis pathway was moderately increased to better accommodate the increased β-carotene pool, resulting in the production level of 809.2 mg/L.

Conclusions: The Y. lipolytica-based β-carotene production chassis was successfully developed through iterative overexpression of multiple pathways, central carbon pathway engineering and lipid pathway flux adjustment. The approach presented here provides insights into future endeavors to improve microbial terpenoid production capability.

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来源期刊
Journal of Biological Engineering
Journal of Biological Engineering BIOCHEMICAL RESEARCH METHODS-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CiteScore
7.10
自引率
1.80%
发文量
32
审稿时长
17 weeks
期刊介绍: Biological engineering is an emerging discipline that encompasses engineering theory and practice connected to and derived from the science of biology, just as mechanical engineering and electrical engineering are rooted in physics and chemical engineering in chemistry. Topical areas include, but are not limited to: Synthetic biology and cellular design Biomolecular, cellular and tissue engineering Bioproduction and metabolic engineering Biosensors Ecological and environmental engineering Biological engineering education and the biodesign process As the official journal of the Institute of Biological Engineering, Journal of Biological Engineering provides a home for the continuum from biological information science, molecules and cells, product formation, wastes and remediation, and educational advances in curriculum content and pedagogy at the undergraduate and graduate-levels. Manuscripts should explore commonalities with other fields of application by providing some discussion of the broader context of the work and how it connects to other areas within the field.
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