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

Hao Luo*, Anne Sofie Lærke Hansen, Lei Yang, Konstantin Schneider, Mette Kristensen, Ulla Christensen, Hanne Bjerre Christensen, Bin Du, Emre Özdemir, Adam M Feist, Jay D Keasling, Michael Krogh Jensen, Markus J Herrgård, Bernhard O Palsson

*Corresponding author for this work

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Abstract

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.
Original languageEnglish
Article numbere2007050
JournalPLOS Biology
Volume17
Issue number3
ISSN1544-9173
DOIs
Publication statusPublished - 2019

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