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Development of a genome-targeting mutator for the adaptive evolution of microbial cells.

Authors
  • Eom, Ga-Eul1
  • Lee, Hyunbin1
  • Kim, Seokhee1
  • 1 Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea. , (North Korea)
Type
Published Article
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Publication Date
Apr 22, 2022
Volume
50
Issue
7
Identifiers
DOI: 10.1093/nar/gkab1244
PMID: 34928386
Source
Medline
Language
English
License
Unknown

Abstract

Methods that can randomly introduce mutations in the microbial genome have been used for classical genetic screening and, more recently, the evolutionary engineering of microbial cells. However, most methods rely on either cell-damaging agents or disruptive mutations of genes that are involved in accurate DNA replication, of which the latter requires prior knowledge of gene functions, and thus, is not easily transferable to other species. In this study, we developed a new mutator for in vivo mutagenesis that can directly modify the genomic DNA. Mutator protein, MutaEco, in which a DNA-modifying enzyme is fused to the α-subunit of Escherichia coli RNA polymerase, increases the mutation rate without compromising the cell viability and accelerates the adaptive evolution of E. coli for stress tolerance and utilization of unconventional carbon sources. This fusion strategy is expected to accommodate diverse DNA-modifying enzymes and may be easily adapted to various bacterial species. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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