关键词: CRISPR-Cas Chromosomal integration Homology-mediated end joining Industrial biotechnology Site-specific recombination Synthetic biology

Mesh : Actinobacteria / genetics Chromosomal Instability Chromosomes Cloning, Molecular / methods Clustered Regularly Interspaced Short Palindromic Repeats DNA End-Joining Repair Escherichia coli / genetics metabolism Gene Dosage Genes Genome, Microbial Homologous Recombination Industrial Microbiology / methods Integrases / genetics metabolism Microorganisms, Genetically-Modified / genetics Multigene Family Synthetic Biology / methods Yeasts / genetics metabolism

来  源:   DOI:10.1016/j.biotechadv.2019.04.002   PDF(Sci-hub)

Abstract:
Industrial biotechnology is reliant on native pathway engineering or foreign pathway introduction for efficient biosynthesis of target products. Chromosomal integration, with intrinsic genetic stability, is an indispensable step for reliable expression of homologous or heterologous genes and pathways in large-scale and long-term fermentation. With advances in synthetic biology and CRISPR-based genome editing approaches, a wide variety of novel enabling technologies have been developed for single-step, markerless, multi-locus genomic integration of large biochemical pathways, which significantly facilitate microbial overproduction of chemicals, pharmaceuticals and other value-added biomolecules. Notably, the newly discovered homology-mediated end joining strategy could be widely applicable for high-efficiency genomic integration in a number of homologous recombination-deficient microbes. In this review, we explore the fundamental principles and characteristics of genomic integration, and highlight the development and applications of targeted integration approaches in the three representative industrial microbial systems, including Escherichia coli, actinomycetes and yeasts.
摘要:
暂无翻译
公众号