A bacterial-derived quorum-sensing platform enables dynamic metabolic control in yeast.

IF 14.9 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Trends in biotechnology Pub Date : 2026-05-05 DOI:10.1016/j.tibtech.2026.04.007

Haotian Zhai, Xinyue Liu, Pinzeng Guo, Yalin Guo, Xiaoyu Yang, Qingsheng Qi, Jens Nielsen, Zihe Liu, Yun Chen, Jin Hou

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引用次数: 0

Abstract

Dynamic regulation of metabolic pathways is critical for optimizing microbial production, yet robust quorum-sensing (QS) systems remain largely unavailable in eukaryotic microorganisms. Here, we establish a bacterial-derived QS platform in Saccharomyces cerevisiae by repurposing the noncanonical RpaI/RpaR system (a LuxI/R-type QS system), which produces p-coumaroyl-homoserine lactone as a signal molecule, bypassing a fundamental metabolic barrier that has prevented functional bacterial QS in eukaryotes. The engineered circuit features low leakage, high sensitivity, and broad dynamic range. By coupling QS with signal amplification and clustered regularly interspaced short palindromic repeats (CRISPR) interference modules, we create a bifunctional cascade system enabling autonomous transcriptional activation and repression. This QS platform enables growth-production decoupling and improves the production of cordycepin, geraniol, and 3-hydroxypropionic acid in both baseline and high-producing strains. Our work establishes a functional bacterial QS system in yeast and expands the synthetic biology toolkit for eukaryotic hosts.

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细菌衍生的群体感应平台使酵母的动态代谢控制成为可能。

代谢途径的动态调节是优化微生物生产的关键，但强大的群体感应（QS）系统在真核微生物中仍然很大程度上不可用。本研究利用非规范RpaI/RpaR系统（一种LuxI/ r型QS系统），在酿酒酵母中建立了细菌衍生的QS平台，该系统产生对coumaroyl-homoserine内酯作为信号分子，绕过了阻止真核生物中功能性细菌QS的基本代谢屏障。该电路具有漏损低、灵敏度高、动态范围宽等特点。通过将QS与信号放大和聚集规律间隔短回文重复序列（CRISPR）干扰模块相结合，我们创建了一个双功能级联系统，能够自主激活和抑制转录。该QS平台实现了生长-生产脱钩，提高了基线菌株和高产菌株的虫草素、香叶醇和3-羟基丙酸的产量。我们的工作在酵母中建立了一个功能性的细菌QS系统，并扩展了真核宿主的合成生物学工具包。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Trends in biotechnology 工程技术-生物工程与应用微生物

CiteScore

28.60

自引率

1.20%

发文量

198

审稿时长

1 months

期刊介绍： Trends in Biotechnology publishes reviews and perspectives on the applied biological sciences, focusing on useful science applied to, derived from, or inspired by living systems. The major themes that TIBTECH is interested in include: Bioprocessing (biochemical engineering, applied enzymology, industrial biotechnology, biofuels, metabolic engineering) Omics (genome editing, single-cell technologies, bioinformatics, synthetic biology) Materials and devices (bionanotechnology, biomaterials, diagnostics/imaging/detection, soft robotics, biosensors/bioelectronics) Therapeutics (biofabrication, stem cells, tissue engineering and regenerative medicine, antibodies and other protein drugs, drug delivery) Agroenvironment (environmental engineering, bioremediation, genetically modified crops, sustainable development).