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

doi:10.1371/journal.pbio.2007050

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

Novo Nordisk Foundation Center for Biosustainability

University of California at San Diego

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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 language	English
Article number	e2007050
Journal	PLOS Biology
Volume	17
Issue number	3
ISSN	1544-9173
DOIs	https://doi.org/10.1371/journal.pbio.2007050
Publication status	Published - 2019

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Luo, H., Hansen, A. S. L., Yang, L., Schneider, K., Kristensen, M., Christensen, U., Christensen, H. B., Du, B., Özdemir, E., Feist, A. M., Keasling, J. D., Jensen, M. K., Herrgård, M. J., & Palsson, B. O. (2019). Coupling S-adenosylmethionine-dependent methylation to growth: Design and uses. PLOS Biology, 17(3), Article e2007050. https://doi.org/10.1371/journal.pbio.2007050

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AU - Luo, Hao

AU - Hansen, Anne Sofie Lærke

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AU - Schneider, Konstantin

AU - Kristensen, Mette

AU - Christensen, Ulla

AU - Christensen, Hanne Bjerre

AU - Du, Bin

AU - Özdemir, Emre

AU - Feist, Adam M

AU - Keasling, Jay D

AU - Jensen, Michael Krogh

AU - Herrgård, Markus J

AU - Palsson, Bernhard O

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AB - 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.

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DO - 10.1371/journal.pbio.2007050

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JO - PLOS Biology

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

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