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.

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

Grant support

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.