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Journal article

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

By Luo, Hao1,2; Hansen, Anne Sofie Lærke1,2,3; Yang, Lei2; Schneider, Konstantin2; Kristensen, Mette2; Christensen, Ulla2,4; Christensen, Hanne Bjerre2; Du, Bin5; Özdemir, Emre1,2; Feist, Adam M2,6,7; Keasling, Jay D2,3; Jensen, Michael Krogh2,3; Herrgård, Markus J1,2,4,8; Palsson, Bernhard O2,7,9 ...and 4 more

Edited by Khosla, Chaitan

From

iLoop, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2

Synthetic Biology Tools for Yeast, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3

Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4

University of California at San Diego5

ALE Technology & Software Development, Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark6

Network Reconstruction in Silico Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark7

Global Econometric Modeling, Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark8

Big Data 2 Knowledge, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark9

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.

Language: English
Publisher: Public Library of Science
Year: 2019
Pages: e2007050
ISSN: 15457885 and 15449173
Types: Journal article
DOI: 10.1371/journal.pbio.2007050
ORCIDs: Luo, Hao , Hansen, Anne Sofie Lærke , Yang, Lei , Schneider, Konstantin , Kristensen, Mette , Christensen, Hanne Bjerre , Özdemir, Emre , Feist, Adam M , Jensen, Michael Krogh , Herrgård, Markus J and Palsson, Bernhard O
Keywords

Biology (General) Catechol O-Methyltransferase Catechol O-Methyltransferase Inhibitors Catechols Methylation Methyltransferases Nitriles QH301-705.5 S-Adenosylmethionine Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Tolcapone entacapone

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