Pathway swapping: Toward modular engineering of essential cellular processes

Niels G.A. Kuijpers, Daniel Solis-Escalante, Marijke A.H. Luttik, Markus M.M. Bisschops, Francine J. Boonekamp, Marcel Van Den Broek, Jack T. Pronk, Jean Marc Daran, Pascale Daran-Lapujade*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

20 Citations (Scopus)


Recent developments in synthetic biology enable one-step implementation of entire metabolic pathways in industrial microorganisms. A similarly radical remodelling of central metabolism could greatly accelerate fundamental and applied research, but is impeded by the mosaic organization of microbial genomes. To eliminate this limitation, we propose and explore the concept of "pathway swapping," using yeast glycolysis as the experimental model. Construction of a "single-locus glycolysis" Saccharomyces cerevisiae platform enabled quick and easy replacement of this yeast's entire complement of 26 glycolytic isoenzymes by any alternative, functional glycolytic pathway configuration. The potential of this approach was demonstrated by the construction and characterization of S. cerevisiae strains whose growth depended on two nonnative glycolytic pathways: a complete glycolysis from the related yeast Saccharomyces kudriavzevii and a mosaic glycolysis consisting of yeast and human enzymes. This work demonstrates the feasibility and potential of modular, combinatorial approaches to engineering and analysis of core cellular processes.

Original languageEnglish
Pages (from-to)15060-15065
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
Publication statusPublished - 27 Dec 2016


  • Glycolysis
  • Modular genomes
  • Pathway swapping
  • Saccharomyces cerevisiae


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