Programming Nutrient Detection with Modular Regulators for Dynamic Control of Microbial Biosynthesis.

IF 3.9 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub Date : 2025-03-21 Epub Date: 2025-03-04 DOI:10.1021/acssynbio.4c00720

Nhu Nguyen, Vincenzo Kennedy, Jung Yeon Lee, Noel Y Chan, Clement T Y Chan

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Abstract

Dynamic control of biosynthetic pathways improves the bioproduction efficiency. One common approach is to use genetic sensors that control pathway expression in response to a nutrient molecule in the target feedstock. However, programming the cellular response requires the engineering of numerous genetic parts, which poses a significant barrier to explore the use of different nutrients as cellular signals. Here we created a dynamic control platform based on a set of modular transcriptional regulators; these regulators control the same promoter for driving gene expression, but each of them responds to a unique signal. We demonstrated that by replacing only the regulator, a different nutrient molecule can then be used for induction of the same genetic circuit. To show host versatility, we implemented this platform in both Escherichia coli and Pseudomonas putida. This platform was then used to program the induction of ethanol production by three nutrients, fructose, cellobiose, and galactose, of which each molecule can be present in a different set of crops. These results suggest that our platform facilitates the use of different agricultural products for the dynamic control of biosynthesis.

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用模块化调节器编程微生物生物合成动态控制的营养检测。

生物合成途径的动态控制提高了生物生产效率。一种常见的方法是使用基因传感器来控制途径表达，以响应目标原料中的营养分子。然而，对细胞反应进行编程需要对许多基因部分进行工程设计，这对探索不同营养物质作为细胞信号的使用构成了重大障碍。在这里，我们创建了一个基于一组模块化转录调控因子的动态控制平台；这些调节因子控制着驱动基因表达的相同启动子，但它们中的每一个都对一个独特的信号作出反应。我们证明，通过仅替换调节器，不同的营养分子可以用于诱导相同的遗传回路。为了显示宿主的多功能性，我们在大肠杆菌和恶臭假单胞菌中实现了这个平台。然后，该平台被用于通过三种营养物质——果糖、纤维素二糖和半乳糖——对乙醇生产的诱导进行编程，其中每种分子都可以存在于不同的作物中。这些结果表明，我们的平台促进了不同农产品对生物合成的动态控制。

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

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.