Biosynthesis of tauro-ursodeoxycholic acid (TUDCA) in Saccharomyces cerevisiae.

IF 4.9 2区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Seonyun Moon, Michael J Smanski
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引用次数: 0

Abstract

Tauroursodeoxycholic acid (TUDCA) is a microbial bile acid known for its diverse yet still largely unexplored biological activities. Traditionally used in Asian medicine, TUDCA and the taurine-free form, ursodeoxycholic acid (UDCA), share similar therapeutic properties. Recent studies suggest that TUDCA is a promising lead compound for developing neuroprotective agents to prevent neurodegenerative diseases such as Parkinson's disease and Huntington's disease. However, sustainable and ethical sources for large-scale TUDCA production remain unavailable. To address this, we are engineering a yeast-based microbial platform capable of producing TUDCA via fermentation. Here we report strains capable of converting the more widely available primary bile acid, chenodeoxycholic acid (CDCA) into TUDCA. This was achieved by introducing heterologous genes enabling taurine conjugation and taurine biosynthesis, providing a sustainable and scalable approach for TUDCA production.

牛头熊去氧胆酸(TUDCA)在酿酒酵母中的生物合成。
牛磺酸去氧胆酸(TUDCA)是一种微生物胆汁酸,以其多样性而闻名,但其生物活性仍未被广泛探索。传统上,TUDCA和不含牛磺酸的熊去氧胆酸(UDCA)在亚洲医学中使用,具有相似的治疗特性。近年来的研究表明,TUDCA是一种有前景的先导化合物,可用于开发神经保护剂,预防帕金森病和亨廷顿病等神经退行性疾病。然而,大规模生产TUDCA的可持续和道德来源仍然不可用。为了解决这个问题,我们正在设计一个基于酵母的微生物平台,能够通过发酵生产TUDCA。在这里,我们报道了能够将更广泛获得的初级胆汁酸,鹅去氧胆酸(CDCA)转化为TUDCA的菌株。这是通过引入异种基因实现牛磺酸偶联和牛磺酸生物合成,为TUDCA的生产提供了可持续和可扩展的方法。
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来源期刊
Microbial Cell Factories
Microbial Cell Factories 工程技术-生物工程与应用微生物
CiteScore
9.30
自引率
4.70%
发文量
235
审稿时长
2.3 months
期刊介绍: Microbial Cell Factories is an open access peer-reviewed journal that covers any topic related to the development, use and investigation of microbial cells as producers of recombinant proteins and natural products, or as catalyzers of biological transformations of industrial interest. Microbial Cell Factories is the world leading, primary research journal fully focusing on Applied Microbiology. The journal is divided into the following editorial sections: -Metabolic engineering -Synthetic biology -Whole-cell biocatalysis -Microbial regulations -Recombinant protein production/bioprocessing -Production of natural compounds -Systems biology of cell factories -Microbial production processes -Cell-free systems
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