Adaptive laboratory evolution of native methanol assimilation in Saccharomyces cerevisiae

Monica I. Espinosa, Ricardo A. Gonzalez-Garcia, Kaspar Valgepea, Manuel R. Plan, Colin Scott, Isak S. Pretorius, Esteban Marcellin, Ian T. Paulsen () and Thomas C. Williams ()
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Monica I. Espinosa: Macquarie University
Ricardo A. Gonzalez-Garcia: The University of Queensland
Kaspar Valgepea: The University of Queensland
Manuel R. Plan: The University of Queensland
Colin Scott: CSIRO Synthetic Biology Future Science Platform
Isak S. Pretorius: Macquarie University
Esteban Marcellin: The University of Queensland
Ian T. Paulsen: Macquarie University
Thomas C. Williams: Macquarie University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Utilising one-carbon substrates such as carbon dioxide, methane, and methanol is vital to address the current climate crisis. Methylotrophic metabolism enables growth and energy generation from methanol, providing an alternative to sugar fermentation. Saccharomyces cerevisiae is an important industrial microorganism for which growth on one-carbon substrates would be relevant. However, its ability to metabolize methanol has been poorly characterised. Here, using adaptive laboratory evolution and 13C-tracer analysis, we discover that S. cerevisiae has a native capacity for methylotrophy. A systems biology approach reveals that global rearrangements in central carbon metabolism fluxes, gene expression changes, and a truncation of the uncharacterized transcriptional regulator Ygr067cp supports improved methylotrophy in laboratory evolved S. cerevisiae. This research paves the way for further biotechnological development and fundamental understanding of methylotrophy in the preeminent eukaryotic model organism and industrial workhorse, S. cerevisiae.

Date: 2020
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DOI: 10.1038/s41467-020-19390-9

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