De novo biosynthesis of β-arbutin in Corynebacterium glutamicum via pathway engineering and process optimization

IF 6.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology for Biofuels Pub Date : 2024-06-25 DOI:10.1186/s13068-024-02540-2
Bin Zhang, Kexin Gou, Kexin Xu, Zhimin Li, Xiaoyan Guo, Xiaoyu Wu
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Abstract

Background

β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin.

Results

This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium.

Conclusions

This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.

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通过途径工程和工艺优化在谷氨酸棒杆菌中重新合成β-熊果苷
背景β-熊果苷是一种对苯二酚葡萄糖苷,存在于梨、熊果树叶和多种植物中,具有抗氧化、抗炎、抗菌和抗癌作用。β-熊果苷在制药和化妆品行业有着广泛的应用。结果本研究通过引入密码子优化的 ubiC、MNX1 和 AS,在谷氨酸球菌 ATCC13032 中建立了 β-熊果苷的生物合成途径。此外,通过进一步使 csm 和 trpE 失活以阻碍竞争性代谢途径,提高了 β-熊果苷的产量滴度。通过进一步改造上游代谢途径和补充 UDP-葡萄糖,最终培育出谷氨酸棒状杆菌 AR11,该菌株在优化发酵培养基中的β-熊果苷生产滴度达到了 7.94 克/升。
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来源期刊
Biotechnology for Biofuels
Biotechnology for Biofuels 工程技术-生物工程与应用微生物
自引率
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审稿时长
2.7 months
期刊介绍: Biotechnology for Biofuels is an open access peer-reviewed journal featuring high-quality studies describing technological and operational advances in the production of biofuels, chemicals and other bioproducts. The journal emphasizes understanding and advancing the application of biotechnology and synergistic operations to improve plants and biological conversion systems for the biological production of these products from biomass, intermediates derived from biomass, or CO2, as well as upstream or downstream operations that are integral to biological conversion of biomass. Biotechnology for Biofuels focuses on the following areas: • Development of terrestrial plant feedstocks • Development of algal feedstocks • Biomass pretreatment, fractionation and extraction for biological conversion • Enzyme engineering, production and analysis • Bacterial genetics, physiology and metabolic engineering • Fungal/yeast genetics, physiology and metabolic engineering • Fermentation, biocatalytic conversion and reaction dynamics • Biological production of chemicals and bioproducts from biomass • Anaerobic digestion, biohydrogen and bioelectricity • Bioprocess integration, techno-economic analysis, modelling and policy • Life cycle assessment and environmental impact analysis
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