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Towards designer organelles by subverting the peroxisomal import pathway

L. Cross,Rupesh Paudyal,Y. Kamisugi,A. Berry,A. Cuming,A. Baker,S. Warriner

Published 2017 in Nature Communications

ABSTRACT

The development of ‘designer’ organelles could be a key strategy to enable foreign pathways to be efficiently controlled within eukaryotic biotechnology. A fundamental component of any such system will be the implementation of a bespoke protein import pathway that can selectively deliver constituent proteins to the new compartment in the presence of existing endogenous trafficking systems. Here we show that the protein–protein interactions that control the peroxisomal protein import pathway can be manipulated to create a pair of interacting partners that still support protein import in moss cells, but are orthogonal to the naturally occurring pathways. In addition to providing a valuable experimental tool to give new insights into peroxisomal protein import, the variant receptor-signal sequence pair forms the basis of a system in which normal peroxisomal function is downregulated and replaced with an alternative pathway, an essential first step in the creation of a designer organelle.Designer organelles could allow the isolation of synthetic biological pathways from endogenous components of the host cell. Here the authors engineer a peroxisomal protein import pathway orthogonal to the naturally occurring system.

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