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利用甘油进行微生物次级代谢产物的生物合成。

Harnessing glycerol for secondary metabolite biosynthesis in microorganisms.

作者信息

Kamasaka Kouhei, Marcello Luiz, Domingues Lucília, Hasunuma Tomohisa

机构信息

Engineering Biology Research Center, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.

Graduate School of Science, Technology and Innovation, Kobe University, 1- 1 Rokkodai, Nada, Kobe, 657-8501, Japan.

出版信息

World J Microbiol Biotechnol. 2025 Sep 15;41(9):325. doi: 10.1007/s11274-025-04537-x.

DOI:10.1007/s11274-025-04537-x
PMID:40952535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12436559/
Abstract

The increase in glycerol availability as a byproduct of biodiesel production has attracted attention in its utilization as a carbon source for microbial fermentation. Compared with traditional carbon sources such as glucose, glycerol enhances the production of various secondary metabolites such as aromatic compounds, polyols, and lipids in microorganisms such as Komagataella phaffii and Yarrowia lipolytica. For instance, in K. phaffii, glycerol increased the titers of p-coumarate, naringenin, and resveratrol compared with glucose-based media, particularly when combined with specific amino acid supplementation. This review presents recent advancements in the production of secondary metabolites from glycerol. The metabolic pathways involved in glycerol utilization and secondary metabolite biosynthesis have been examined with insights into the regulation of these processes. The potential applications of glycerol-derived secondary metabolites in the pharmaceutical, food, and biofuel industries have been discussed. Finally, the challenges such as strain robustness, variability in crude glycerol quality, and downstream processing have been addressed with focus on recent innovations in metabolic engineering, redox tuning, and bioprocess control. Overall, this review highlights the potential of glycerol in the context of these advancements as a sustainable and cost-effective feedstock for the next-generation microbial biomanufacturing of high-value secondary metabolites.

摘要

作为生物柴油生产的副产物,甘油可用性的增加引发了人们对其作为微生物发酵碳源加以利用的关注。与葡萄糖等传统碳源相比,甘油能提高诸如毕赤酵母和解脂耶氏酵母等微生物中各种次级代谢产物的产量,如芳香族化合物、多元醇和脂质。例如,在毕赤酵母中,与基于葡萄糖的培养基相比,甘油提高了对香豆酸、柚皮素和白藜芦醇的滴度,特别是在补充特定氨基酸时。本综述介绍了利用甘油生产次级代谢产物的最新进展。研究了甘油利用和次级代谢产物生物合成所涉及的代谢途径,并深入了解了这些过程的调控机制。讨论了甘油衍生的次级代谢产物在制药、食品和生物燃料行业的潜在应用。最后,针对菌株稳健性、粗甘油质量变异性和下游加工等挑战,重点介绍了代谢工程、氧化还原调节和生物过程控制方面的最新创新。总体而言,本综述强调了在这些进展背景下,甘油作为高价值次级代谢产物下一代微生物生物制造的可持续且经济高效原料的潜力。

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本文引用的文献

1
The physiology of an engineered Saccharomyces cerevisiae strain that carries both an improved glycerol-3-phosphate and the synthetic dihydroxyacetone pathway for glycerol utilization.一种工程化酿酒酵母菌株的生理学特性,该菌株同时具有改进的甘油-3-磷酸途径和用于甘油利用的合成二羟基丙酮途径。
FEMS Yeast Res. 2025 Jan 30;25. doi: 10.1093/femsyr/foaf015.
2
Acetol biosynthesis enables NADPH balance during nitrogen limitation in engineered Escherichia coli.在工程化大肠杆菌中,丙酮醇生物合成可在氮限制期间实现NADPH平衡。
Microb Cell Fact. 2025 Mar 16;24(1):65. doi: 10.1186/s12934-025-02687-z.
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Environmental impacts of valorisation of crude glycerol from biodiesel production - A life cycle perspective.
从生命周期角度看生物柴油生产中粗甘油增值的环境影响。
Waste Manag. 2024 Apr 30;179:55-65. doi: 10.1016/j.wasman.2024.03.005. Epub 2024 Mar 9.
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Application of New Transformants in Production of Citrates and Erythritol from Glycerol.新型转化体在甘油生产柠檬酸和赤藓糖醇中的应用。
Int J Mol Sci. 2024 Jan 25;25(3):1475. doi: 10.3390/ijms25031475.
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Aromatic secondary metabolite production from glycerol was enhanced by amino acid addition in Pichia pastoris.氨基酸添加可提高毕赤酵母中甘油的芳香族次生代谢产物的产量。
Appl Microbiol Biotechnol. 2023 Dec;107(24):7391-7401. doi: 10.1007/s00253-023-12798-5. Epub 2023 Sep 27.
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Microbial Secondary Metabolites via Fermentation Approaches for Dietary Supplementation Formulations.微生物发酵法生产的次生代谢产物作为膳食补充配方。
Molecules. 2023 Aug 11;28(16):6020. doi: 10.3390/molecules28166020.
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From Nature to Lab: A Review of Secondary Metabolite Biosynthetic Pathways, Environmental Influences, and In Vitro Approaches.从自然到实验室:次生代谢物生物合成途径、环境影响及体外方法综述
Metabolites. 2023 Jul 28;13(8):895. doi: 10.3390/metabo13080895.
8
Continuous production of succinic acid from glycerol: A complete experimental and computational study.连续生产琥珀酸:甘油的完整实验和计算研究。
Bioresour Technol. 2023 Oct;386:129518. doi: 10.1016/j.biortech.2023.129518. Epub 2023 Jul 20.
9
Production of secondary metabolites using tissue culture-based biotechnological applications.利用基于组织培养的生物技术应用生产次生代谢产物。
Front Plant Sci. 2023 Jun 29;14:1132555. doi: 10.3389/fpls.2023.1132555. eCollection 2023.
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Int J Mol Sci. 2023 Apr 26;24(9):7889. doi: 10.3390/ijms24097889.