De Novo Biosynthesis of a Bioactive Meroterpene Bakuchiol in Yeast

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

ACS Synthetic Biology Pub Date : 2024-10-30 DOI:10.1021/acssynbio.4c0041610.1021/acssynbio.4c00416

Yi-Lei Zheng, Ye Xu, Yan-Qiu Liu, Qing-Wei Zhao and Yong-Quan Li*,

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引用次数: 0

Abstract

Bakuchiol (BAK), a specialized meroterpene, is known for its valuable biological properties and has recently gained prominence in cosmetology for its retinol-like functionality. However, low abundance in natural sources leads to environmentally unfriendly and unsustainable practices associated with crop-based manufacturing and chemical synthesis. Here, we identified a prenyltransferase (PT) from Psoralea corylifolia that catalyzes the reverse geranylation of a nonaromatic carbon in para-coumaric acid (p-CA), coupled with a decarboxylation step to form BAK. Given that the biosynthesis pathway of BAK is well elucidated, we engineered Saccharomyces cerevisiae to produce BAK, starting from glucose. To enhance the titer of BAK, we employed a multifaceted approach that included increasing the supply of precursors, balancing the fluxes in the two parallel biosynthetic pathways, engineering of prenyltransferase, and fusing enzymes. Consequently, the engineered yeast strains showed a marked improvement of 117.3-fold in BAK production, reaching a titer of 9.28 mg/L from glucose. Our work provides a viable approach for the sustainable microbial production of complex natural meroterpenes.

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酵母从头合成具有生物活性的 Meroterpene Bakuchiol

巴克烯二醇（BAK）是一种特殊的经萜烯类化合物，因其宝贵的生物特性而闻名，最近又因其类似视黄醇的功能而在美容领域大放异彩。然而，由于天然来源的丰度较低，导致以农作物为基础的生产和化学合成方法对环境不友好且不可持续。在这里，我们从茜草中发现了一种前酰基转移酶（PT），它能催化对位香豆酸（p-CA）中一个非芳香族碳的反向香叶酯化作用，并通过脱羧步骤形成 BAK。鉴于 BAK 的生物合成途径已被充分阐明，我们改造了酿酒酵母，使其从葡萄糖开始生产 BAK。为了提高 BAK 的滴度，我们采用了一种多方面的方法，包括增加前体的供应、平衡两条平行生物合成途径的通量、前酰转移酶的工程化以及酶的融合。结果，工程酵母菌株的 BAK 产量明显提高了 117.3 倍，葡萄糖滴度达到 9.28 毫克/升。我们的工作为复杂天然美拉德萜烯的可持续微生物生产提供了一种可行的方法。

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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.