在酿酒酵母发酵过程中建立热敏代谢调控策略以提高α-双abolene产量

IF 3.9 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Pan Feng, Bowen Sun, Haoran Bi, Yufei Bao, Meng Wang*, Huili Zhang and Yunming Fang, 
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引用次数: 0

摘要

α-双abolene独特的香气在香水和化妆品中被高度重视,而其抗氧化性能具有重要的制药潜力。然而,由于细胞生长限制和α-双abolene前体焦磷酸法尼酯供应不足,在酿酒酵母中生产α-双abolene仍然是一个突出的挑战。本文报道了一株能高产α-双abolene的酿酒葡萄球菌平台菌株。甲羟戊酸代谢途径的迭代增强使α-双abolene合成途径中的碳通量最大化。MVA途径中间体对细胞生长的影响通过基于温度敏感调节策略控制的两阶段发酵来解决。通过代谢组学和响应面模型分析对发酵培养基进行优化。在最优发酵工艺下,分批补料发酵时α-双abolene的滴度达到18.6 g/L,为目前报道的最高滴度。这些策略为工业规模的萜烯生物合成开辟了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Developing Thermosensitive Metabolic Regulation Strategies in the Fermentation Process of Saccharomyces cerevisiae to Enhance α-Bisabolene Production

Developing Thermosensitive Metabolic Regulation Strategies in the Fermentation Process of Saccharomyces cerevisiae to Enhance α-Bisabolene Production

α-Bisabolene’s distinctive aroma is highly prized in fragrances and cosmetics, while its antioxidant properties hold significant pharmaceutical potential. However, the production of α-bisabolene in Saccharomyces cerevisiae remains an outstanding challenge due to cell growth limitations and insufficient supply of the α-bisabolene precursor farnesyl pyrophosphate. In this work, a new S. cerevisiae platform strain capable of producing high levels of α-bisabolene was presented. Carbon flux in the α-bisabolene synthesis pathway was maximized by iterative enhancement of the mevalonate metabolic pathway. The effects of MVA pathway intermediates on cell growth were addressed through a two-stage fermentation controlled based on a temperature-sensitive regulation strategy. The fermentation medium was optimized based on metabolomics and response surface model analysis. Under the optimal fermentation process, the titer of α-bisabolene reached 18.6 g/L during fed-batch fermentation, representing the highest titer reported to date. These strategies open up new avenues for industrial-scale terpene biosynthesis.

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来源期刊
CiteScore
8.00
自引率
10.60%
发文量
380
审稿时长
6-12 weeks
期刊介绍: The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.
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