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Pathway swapping: Toward modular engineering of essential cellular processes.

ABSTRACT: 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.

SUBMITTER: Kuijpers NG

PROVIDER: S-EPMC5206561 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Pathway swapping: Toward modular engineering of essential cellular processes.

Kuijpers Niels G A NG Solis-Escalante Daniel D Luttik Marijke A H MA Bisschops Markus M M MM Boonekamp Francine J FJ van den Broek Marcel M Pronk Jack T JT Daran Jean-Marc JM Daran-Lapujade Pascale P

Proceedings of the National Academy of Sciences of the United States of America 20161212 52

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" Saccharomy ...[more]

PMID: 27956602

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Project description:A variety of biological networks can be modeled as logical or Boolean networks. However, a simplification of the reality to binary states of the nodes does not ease the difficulty of analyzing the dynamics of large, complex networks, such as signal transduction networks, due to the exponential dependence of the state space on the number of nodes. This paper considers a recently introduced method for finding a fairly small subnetwork, representing a collection of nodes that determine the states of most other nodes with a reasonable level of entropy. The subnetwork contains the most determinative nodes that yield the highest information gain. One of the goals of this paper is to propose an algorithm for finding a suitable subnetwork size. The information gain is quantified by the so-called determinative power of the nodes, which is obtained via the mutual information, a concept originating in information theory. We find the most determinative nodes for 36 network models available in the online database Cell Collective (http://cellcollective.org). We provide statistical information that indicates a weak correlation between the subnetwork size and other variables, such as network size, or maximum and average determinative power of nodes. We observe that the proportion represented by the subnetwork in comparison to the whole network shows a weak tendency to decrease for larger networks. The determinative power of nodes is weakly correlated to the number of outputs of a node, and it appears to be independent of other topological measures such as closeness or betweenness centrality. Once the subnetwork of the most determinative nodes is identified, we generate a biological function analysis of its nodes for some of the 36 networks. The analysis shows that a large fraction of the most determinative nodes are essential and involved in crucial biological functions. The biological pathway analysis of the most determinative nodes shows that they are involved in important disease pathways.

Dataset Information

Pathway swapping: Toward modular engineering of essential cellular processes.

Publications

Pathway swapping: Toward modular engineering of essential cellular processes.

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