Replacement of Thymidine by a Modified Base in the Escherichia coli Genome

Angad P. Mehta; Han Li; Sean A. Reed; Lubica Supekova; Tsotne Javahishvili; Peter G. Schultz

doi:10.1021/jacs.6b03904

Replacement of Thymidine by a Modified Base in the Escherichia coli Genome

Angad P. Mehta, Han Li, Sean A. Reed, Lubica Supekova, Tsotne Javahishvili, Peter G. Schultz

Research output: Contribution to journal › Article › peer-review

Abstract

Prokaryotic and eukaryotic genomic DNA is comprised of the four building blocks A, G, C, and T. We have begun to explore the consequences of replacing a large fraction or all of a nucleoside in genomic DNA with a modified nucleoside. As a first step we have investigated the possibility of replacement of T by 2′-deoxy-5-(hydroxymethyl)uridine (5hmU) in the genomic DNA of Escherichia coli. Metabolic engineering with phage genes followed by random mutagenesis enabled us to achieve approximately 75% replacement of T by 5hmU in the E. coli genome and in plasmids.

Original language	English (US)
Pages (from-to)	7272-7275
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	138
Issue number	23
DOIs	https://doi.org/10.1021/jacs.6b03904
State	Published - Jun 15 2016
Externally published	Yes

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.6b03904

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AU - Supekova, Lubica

AU - Javahishvili, Tsotne

AU - Schultz, Peter G.

PY - 2016/6/15

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AB - Prokaryotic and eukaryotic genomic DNA is comprised of the four building blocks A, G, C, and T. We have begun to explore the consequences of replacing a large fraction or all of a nucleoside in genomic DNA with a modified nucleoside. As a first step we have investigated the possibility of replacement of T by 2′-deoxy-5-(hydroxymethyl)uridine (5hmU) in the genomic DNA of Escherichia coli. Metabolic engineering with phage genes followed by random mutagenesis enabled us to achieve approximately 75% replacement of T by 5hmU in the E. coli genome and in plasmids.

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Replacement of Thymidine by a Modified Base in the Escherichia coli Genome

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