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

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...

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Bibliographic Details
Published in:	PLoS biology Vol. 17; no. 3; p. e2007050
Main Authors:	Luo, Hao, Hansen, Anne Sofie L, Yang, Lei, Schneider, Konstantin, Kristensen, Mette, Christensen, Ulla, Christensen, Hanne B, Du, Bin, Özdemir, Emre, Feist, Adam M, Keasling, Jay D, Jensen, Michael K, Herrgård, Markus J, Palsson, Bernhard O
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 11-03-2019 Public Library of Science (PLoS)
Subjects:	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 Denmark La Jolla California California United States > US
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AC02-05CH11231 USDOE Office of Science (SC) I have read the journal's policy, and the authors of this manuscript have the following competing interests. Luo H. is an inventor of the patent applications WO2017202897 and WO2018108966. Luo H. and Hansen A. S. L. are inventors of the patent application WO2018037098.
ISSN:	1545-7885 1544-9173 1545-7885
DOI:	10.1371/journal.pbio.2007050