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Coupling S-adenosylmethionine–dependent methylation to growth: Design and uses

by Kristensen, Mette , Christensen, Hanne B. , Luo, Hao , Keasling, Jay D. , Du, Bin , Hansen, Anne Sofie L. , Feist, Adam M. , Yang, Lei , Schneider, Konstantin , Christensen, Ulla , Herrgård, Markus J. , Özdemir, Emre , Palsson, Bernhard O. , Jensen, Michael K.

in Acetyltransferase / Adenosylmethionine / BASIC BIOLOGICAL SCIENCES / Bioengineering / Biology and Life Sciences / Catechol / Catechol O-methyltransferase / Catechol O-Methyltransferase - metabolism / Catechol O-Methyltransferase Inhibitors - pharmacology / Catechols - pharmacology / Chromosomes / Cloning / CRISPR / Deoxyribonucleic acid / Design / DNA / DNA methylation / E coli / Engineering / Enzymatic activity / Enzymes / Evolution / Gene expression / Genomes / Homocysteine / Laboratories / Medicine and Health Sciences / Metabolism / Metabolites / Methionine / Methods / Methods and Resources / Methylation / Methyltransferase / Methyltransferases - metabolism / Mutation / Nitriles - pharmacology / Observations / Physical Sciences / Physiological aspects / Research and Analysis Methods / S-Adenosylmethionine / S-Adenosylmethionine - metabolism / Saccharomyces cerevisiae / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae Proteins - metabolism / Sulfur / Supervision / Systems design / Tolcapone / Tolcapone - pharmacology

2019

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Coupling S-adenosylmethionine–dependent methylation to growth: Design and uses

2019

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2019

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Journal Article

Coupling S-adenosylmethionine–dependent methylation to growth: Design and uses

Kristensen, Mette,

Christensen, Hanne B.,

Luo, Hao,

Keasling, Jay D.,

Du, Bin,

Hansen, Anne Sofie L.,

Feist, Adam M.,

Yang, Lei,

Schneider, Konstantin,

Christensen, Ulla,

Herrgård, Markus J.,

Özdemir, Emre,

Palsson, Bernhard O.,

Jensen, Michael K.

2019

Overview

We present a selection design that couples S-adenosylmethionine-dependent methylation to growth. We demonstrate its use in improving the enzyme activities of not only N-type and O-type methyltransferases by 2-fold but also an acetyltransferase of another enzyme category when linked to a methylation pathway in Escherichia coli using adaptive laboratory evolution. We also demonstrate its application for drug discovery using a catechol O-methyltransferase and its inhibitors entacapone and tolcapone. Implementation of this design in Saccharomyces cerevisiae is also demonstrated.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Acetyltransferase

/ Adenosylmethionine

/ BASIC BIOLOGICAL SCIENCES

/ Bioengineering

/ Biology and Life Sciences

/ Catechol

/ Catechol O-methyltransferase