{"title":"乙酸胁迫和利用协同促进甘油酸根念珠菌角鲨烯的生物合成","authors":"","doi":"10.1016/j.bej.2024.109413","DOIUrl":null,"url":null,"abstract":"<div><p>Squalene is widely used in industries such as vaccines and cosmetics. The traditional carbon source for microbial synthesis of squalene is glucose, but its long metabolic pathway leads to inefficient synthesis, limiting industrial production. This study uses acetate as a carbon source, taking advantage of its stress effects and the ability to shorten metabolic pathways to enhance the synthesis of squalene. To promote the accumulation of squalene, the MVA pathway and NADPH supply pathways were enhanced. To alleviate acetic acid stress, acetic acid conversion was accelerated by overexpressing <em>ACS1</em>, and the strain’s tolerance to acetic acid was improved by overexpressing <em>HOG1</em>. Subsequently, the strain was subjected to fed-batch fermentation under acetic acid stress with a carbon source of 6 g/L acetic acid, resulting in a squalene titer of 1834.74 mg/L in shake flasks. The culmination of these strategies, applied during a 96 h fed-batch fermentation with acetic acid-mediated pH control in a 5 L bioreactor, resulted in a squalene titer of 8.76 g/L, a content of 411.24 mg/g DCW, and a productivity of 4.28 mg·h<sup>−1</sup>·g<sup>−1</sup> DCW, marking the highest productivity reported to date. This study provides a novel perspective for the green, economically efficient biosynthesis of squalene.</p></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Acetic acid stress and utilization synergistically enhance squalene biosynthesis in Candida glycerinogenes\",\"authors\":\"\",\"doi\":\"10.1016/j.bej.2024.109413\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Squalene is widely used in industries such as vaccines and cosmetics. The traditional carbon source for microbial synthesis of squalene is glucose, but its long metabolic pathway leads to inefficient synthesis, limiting industrial production. This study uses acetate as a carbon source, taking advantage of its stress effects and the ability to shorten metabolic pathways to enhance the synthesis of squalene. To promote the accumulation of squalene, the MVA pathway and NADPH supply pathways were enhanced. To alleviate acetic acid stress, acetic acid conversion was accelerated by overexpressing <em>ACS1</em>, and the strain’s tolerance to acetic acid was improved by overexpressing <em>HOG1</em>. Subsequently, the strain was subjected to fed-batch fermentation under acetic acid stress with a carbon source of 6 g/L acetic acid, resulting in a squalene titer of 1834.74 mg/L in shake flasks. The culmination of these strategies, applied during a 96 h fed-batch fermentation with acetic acid-mediated pH control in a 5 L bioreactor, resulted in a squalene titer of 8.76 g/L, a content of 411.24 mg/g DCW, and a productivity of 4.28 mg·h<sup>−1</sup>·g<sup>−1</sup> DCW, marking the highest productivity reported to date. This study provides a novel perspective for the green, economically efficient biosynthesis of squalene.</p></div>\",\"PeriodicalId\":8766,\"journal\":{\"name\":\"Biochemical Engineering Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical Engineering Journal\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1369703X24002006\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical Engineering Journal","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1369703X24002006","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Acetic acid stress and utilization synergistically enhance squalene biosynthesis in Candida glycerinogenes
Squalene is widely used in industries such as vaccines and cosmetics. The traditional carbon source for microbial synthesis of squalene is glucose, but its long metabolic pathway leads to inefficient synthesis, limiting industrial production. This study uses acetate as a carbon source, taking advantage of its stress effects and the ability to shorten metabolic pathways to enhance the synthesis of squalene. To promote the accumulation of squalene, the MVA pathway and NADPH supply pathways were enhanced. To alleviate acetic acid stress, acetic acid conversion was accelerated by overexpressing ACS1, and the strain’s tolerance to acetic acid was improved by overexpressing HOG1. Subsequently, the strain was subjected to fed-batch fermentation under acetic acid stress with a carbon source of 6 g/L acetic acid, resulting in a squalene titer of 1834.74 mg/L in shake flasks. The culmination of these strategies, applied during a 96 h fed-batch fermentation with acetic acid-mediated pH control in a 5 L bioreactor, resulted in a squalene titer of 8.76 g/L, a content of 411.24 mg/g DCW, and a productivity of 4.28 mg·h−1·g−1 DCW, marking the highest productivity reported to date. This study provides a novel perspective for the green, economically efficient biosynthesis of squalene.
期刊介绍:
The Biochemical Engineering Journal aims to promote progress in the crucial chemical engineering aspects of the development of biological processes associated with everything from raw materials preparation to product recovery relevant to industries as diverse as medical/healthcare, industrial biotechnology, and environmental biotechnology.
The Journal welcomes full length original research papers, short communications, and review papers* in the following research fields:
Biocatalysis (enzyme or microbial) and biotransformations, including immobilized biocatalyst preparation and kinetics
Biosensors and Biodevices including biofabrication and novel fuel cell development
Bioseparations including scale-up and protein refolding/renaturation
Environmental Bioengineering including bioconversion, bioremediation, and microbial fuel cells
Bioreactor Systems including characterization, optimization and scale-up
Bioresources and Biorefinery Engineering including biomass conversion, biofuels, bioenergy, and optimization
Industrial Biotechnology including specialty chemicals, platform chemicals and neutraceuticals
Biomaterials and Tissue Engineering including bioartificial organs, cell encapsulation, and controlled release
Cell Culture Engineering (plant, animal or insect cells) including viral vectors, monoclonal antibodies, recombinant proteins, vaccines, and secondary metabolites
Cell Therapies and Stem Cells including pluripotent, mesenchymal and hematopoietic stem cells; immunotherapies; tissue-specific differentiation; and cryopreservation
Metabolic Engineering, Systems and Synthetic Biology including OMICS, bioinformatics, in silico biology, and metabolic flux analysis
Protein Engineering including enzyme engineering and directed evolution.