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

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub 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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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.