Journal
ACS SYNTHETIC BIOLOGY
Volume 8, Issue 9, Pages 2141-2151Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.9b00218
Keywords
transposable elements; insertion sequence; IS1; IS10; Escherichia coli; stress; proteomics; synthetic biology
Categories
Funding
- EPSRC [EP/M002403/1, EP/N009746/1]
- China Regenerative Medicine International Ltd.
- EPSRC [EP/N009746/1, EP/M002403/1] Funding Source: UKRI
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It has been widely debated whether transposable elements have a positive or a negative effect on their host cells. This study demonstrated that transposable elements, specifically insertion sequences (ISs), can adopt a defensive role in Escherichia coli. In three different E. coli strains (S17, DH5 alpha, and Nissle 1917), IS1 and IS10 rapidly disrupted the I-CeuI gene (encoding I-CeuI endonuclease) on the plasmid pLO11-ICeuI as early as the first generation, despite the gene-circuit being under control of an arabinose promoter. Proteomics analysis showed that the protein abundance profile of E. coli DH5 alpha with pLO11-ICeuI in the fifth generation was nearly opposite to that of control strain (E. coli with pLO11, no I-CeuI). The DNA damage caused by the leaky expression of I-CeuI was enough to trigger a SOS response and alter lipid synthesis, ribosomal activity, RNA/DNA metabolism, central dogma and cell cycle processes in E. coli DH5 alpha. After the ISs disrupted the expression of I-CeuI, cells fully recovered by the 31st generation had a protein abundance profile similar to that of the control strain. This study showed that ISs readily mutated a harmful gene which subsequently restored host fitness. These observations have implications for the stability of designed gene circuits in synthetic biology.
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