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

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

doi:10.1371/journal.pbio.2007050

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

PLoS Biol. 2019 Mar 11;17(3):e2007050. doi: 10.1371/journal.pbio.2007050. eCollection 2019 Mar.

Authors

Hao Luo¹, Anne Sofie L Hansen¹, Lei Yang¹, Konstantin Schneider¹, Mette Kristensen¹, Ulla Christensen¹, Hanne B Christensen¹, Bin Du², Emre Özdemir¹, Adam M Feist^{1

2}, Jay D Keasling^{1

3

4

5

6}, Michael K Jensen¹, Markus J Herrgård¹, Bernhard O Palsson^{1

2

7}

Affiliations

¹ Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
² Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America.
³ Joint BioEnergy Institute, Emeryville, California, United States of America.
⁴ Center for Synthetic Biochemistry, Institute for Synthetic Biology, Shenzhen Institutes of Advanced Technologies, Shenzhen, China.
⁵ Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
⁶ Department of Chemical and Biomolecular Engineering and Department of Bioengineering, University of California, Berkeley, California, United States of America.
⁷ Department of Pediatrics, University of California, San Diego, La Jolla, California, United States of America.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catechol O-Methyltransferase / metabolism
Catechol O-Methyltransferase Inhibitors / pharmacology
Catechols / pharmacology
Methylation
Methyltransferases / metabolism
Nitriles / pharmacology
S-Adenosylmethionine / metabolism*
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / metabolism*
Tolcapone / pharmacology

Substances

Catechol O-Methyltransferase Inhibitors
Catechols
Nitriles
Saccharomyces cerevisiae Proteins
entacapone
S-Adenosylmethionine
Tolcapone
Methyltransferases
Catechol O-Methyltransferase

Grants and funding

Novo Nordisk Foundation http://novonordiskfonden.dk/en (grant number NNF10CC1016517). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.