A self-regulated network for dynamically balancing multiple precursors in complex biosynthetic pathways.

Autor: Zou Y; School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA., Zhang J; School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA., Wang J; School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA., Gong X; School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA., Jiang T; School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA., Yan Y; School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA. Electronic address: yajunyan@uga.edu.
Jazyk: angličtina
Zdroj: Metabolic engineering [Metab Eng] 2024 Mar; Vol. 82, pp. 69-78. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1016/j.ymben.2024.02.001
Abstrakt: Microbial synthesis has emerged as a promising and sustainable alternative to traditional chemical synthesis and plant extraction. However, the competition between synthetic pathways and central metabolic pathways for cellular resources may impair final production efficiency. Moreover, when the synthesis of target product requires multiple precursors from the same node, the conflicts of carbon flux have further negative impacts on yields. In this study, a self-regulated network was developed to relieve the competition of precursors in complex synthetic pathways. Using 4-hydroxycoumarin (4-HC) synthetic pathway as a proof of concept, we employed an intermediate as a trigger to dynamically rewire the metabolic flux of pyruvate and control the expression levels of genes in 4-HC synthetic pathway, achieving self-regulation of multiple precursors and enhanced titer. Transcriptomic analysis results additionally demonstrated that the gene transcriptional levels of both pyruvate kinase PykF and synthetic pathway enzyme SdgA dynamically changed according to the intermediate concentrations. Overall, our work established a self-regulated network to dynamically balance the metabolic flux of two precursors in 4-HC biosynthesis, providing insight into balancing biosynthetic pathways where multiple precursors compete and interfere with each other.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2024 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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