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Global rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative.

Zongjie Dai | Mingtao Huang | Yun Chen | Verena Siewers | Jens Nielsen
Nature communications | 2018

Saccharomyces cerevisiae is a Crabtree-positive eukaryal model organism. It is believed that the Crabtree effect has evolved as a competition mechanism by allowing for rapid growth and production of ethanol at aerobic glucose excess conditions. This inherent property of yeast metabolism and the multiple mechanisms underlying it require a global rewiring of the entire metabolic network to abolish the Crabtree effect. Through rational engineering of pyruvate metabolism combined with adaptive laboratory evolution (ALE), we demonstrate that it is possible to obtain such a global rewiring and hereby turn S. cerevisiae into a Crabtree-negative yeast. Using integrated systems biology analysis, we identify that the global rewiring of cellular metabolism is accomplished through a mutation in the RNA polymerase II mediator complex, which is also observed in cancer cells expressing the Warburg effect.

Pubmed ID: 30076310

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SGD Gene Ontology Slim Mapper (tool)

RRID:SCR_005784

The GO Slim Mapper (aka GO Term Mapper) maps the specific, granular GO terms used to annotate a list of budding yeast gene products to corresponding more general parent GO slim terms. Uses the SGD GO Slim sets. Three GO Slim sets are available at SGD: * Macromolecular complex terms: protein complex terms from the Cellular Component ontology * Yeast GO-Slim: GO terms that represent the major Biological Processes, Molecular Functions, and Cellular Components in S. cerevisiae * Generic GO-Slim: broad, high level GO terms from the Biological Process and Cellular Component ontologies selected and maintained by the Gene Ontology Consortium (GOC) Platform: Online tool

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MP Biomedicals (tool)

RRID:SCR_013308

An Antibody supplier

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GenScript (tool)

RRID:SCR_002891

Commercial organization which provides life science services and products to researchers. They specialize in gene synthesis, peptide, protein, antibody and preclinical drug development service.

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