Improving the Intensity of Integrated Expression for Microbial Production

IF 3.7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Zi-Kai Wang, Jin-Song Gong*, Jiufu Qin, Hui Li, Zhen-Ming Lu, Jin-Song Shi, Zheng-Hong Xu
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引用次数: 5

Abstract

Chromosomal integration of exogenous genes is preferred for industrially related fermentation, as plasmid-mediated fermentation leads to extra metabolic burden and genetic instability. Moreover, with the development and advancement of genome engineering and gene editing technologies, inserting genes into chromosomes has become more convenient; integration expression is extensively utilized in microorganisms for industrial bioproduction and expected to become the trend of recombinant protein expression. However, in actual research and application, it is important to enhance the expression of heterologous genes at the host genome level. Herein, we summarized the basic principles and characteristics of genomic integration; furthermore, we highlighted strategies to improve the expression of chromosomal integration of genes and pathways in host strains from three aspects, including chassis cell optimization, regulation of expression elements in gene expression cassettes, optimization of gene dose level and integration sites on chromosomes. Moreover, we reviewed and summarized the relevant studies on the application of integrated expression in the exploration of gene function and the various types of industrial microorganism production. Consequently, this review would serve as a reference for the better application of integrated expression.

Abstract Image

提高微生物生产的整合表达强度
由于质粒介导的发酵会导致额外的代谢负担和遗传不稳定,因此外源基因的染色体整合是工业相关发酵的首选。此外,随着基因组工程和基因编辑技术的发展和进步,将基因插入染色体变得更加方便;整合表达在工业生物生产中得到了广泛的应用,有望成为重组蛋白表达的发展趋势。然而,在实际的研究和应用中,在宿主基因组水平上增强外源基因的表达是非常重要的。本文综述了基因组整合的基本原理和特点;此外,我们从底盘细胞优化、基因表达盒中表达元件的调控、基因剂量水平的优化和染色体上整合位点的优化三个方面阐述了提高宿主菌株染色体整合基因和途径表达的策略。同时,对整合表达在基因功能探索和各类工业微生物生产中的相关研究进行了综述和总结。为更好地应用综合表达提供参考。
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来源期刊
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.
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