De Novo Biosynthesis of a Polyene-Type Ginsenoside Precursor Dammaradienol in Saccharomyces cerevisiae.

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

ACS Synthetic Biology Pub Date : 2024-12-20 Epub Date: 2024-11-20 DOI:10.1021/acssynbio.4c00396

Yuhong Gan, Zhengping Li, Baolian Fan, Zhongju Ji, Lu Yang, Yuhong Wu, Qiongyu Ye, Aijia Ji, Zhongqiu Liu, Lixin Duan

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引用次数: 0

Abstract

Typical dammarane-type ginsenosides are well-known tetracyclic triterpenoids with significant pharmacological effects including antitumor, cardiovascular protection, and neuroprotection. Polyene-type ginsenosides exhibit stronger biological activities than common ginsenosides; however, their contents are low, and most are converted from ginsenosides through a series of processing steps, resulting in higher preparation costs. In this study, a dammaradienol synthase, AarOSC20433, was identified for the first time from Artemisia argyi H. Lév. & Vaniot (A. argyi). The high-yielding squalene strain constructed in this study was used as the chassis strain. Yeast heterologous biosynthesis of the polyene-type ginsenoside precursor dammaradienol was achieved via metabolic engineering strategies, including optimization of the terpene supply, increase in copy number of AarOSC20433, and rational enzyme design. Eventually, through replenishment and batch fermentation, the titer of dammaradienol reached 1.037 g/L (4.3 mg/L/OD), laying a solid foundation for the construction of a polyene-type ginsenoside cell factory.

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在酿酒酵母中从头合成多烯型人参皂苷前体达玛二烯醇

典型的达玛烷人参皂甙是著名的四环三萜类化合物，具有显著的药理作用，包括抗肿瘤、保护心血管和神经。与普通人参皂甙相比，多烯型人参皂甙具有更强的生物活性，但其含量较低，而且大多是由人参皂甙经过一系列加工步骤转化而来，制备成本较高。本研究首次从阿尔基蒿 H. Lév. & Vaniot （Artemisia argyi H. Lév. & Vaniot）中发现了一种达玛二烯醇合成酶 AarOSC20433。Lév. & Vaniot（A. argyi）中首次发现了一种达玛二烯醇合成酶 AarOSC20433。本研究中构建的高产角鲨烯菌株被用作基质菌株。通过优化萜烯供应、增加 AarOSC20433 的拷贝数和合理的酶设计等代谢工程策略，实现了多烯型人参皂苷前体达玛二烯醇的酵母异源生物合成。最终，通过补充和批量发酵，达玛二烯醇的滴度达到了1.037克/升（4.3毫克/升/OD），为构建多烯型人参皂苷细胞工厂奠定了坚实的基础。

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来源期刊

ACS Synthetic Biology 生物-

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.