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  • Perspective
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Harnessing yeast organelles for metabolic engineering

Nature Chemical Biology volume 13, pages 823–832 (2017)Cite this article

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Abstract

Each subcellular compartment in yeast offers a unique physiochemical environment and metabolite, enzyme, and cofactor composition. While yeast metabolic engineering has focused on assembling pathways in the cell cytosol, there is growing interest in embracing subcellular compartmentalization. Beyond harnessing distinct organelle properties, physical separation of organelles from the cytosol has the potential to eliminate metabolic crosstalk and enhance compartmentalized pathway efficiency. In this Perspective we review the state of the art in yeast subcellular engineering, highlighting the benefits of targeting biosynthetic pathways to subcellular compartments, including mitochondria, peroxisomes, the ER and/or Golgi, vacuoles, and the cell wall, in different yeast species. We compare the performances of strains developed with subcellular engineering to those of native producers or yeast strains previously engineered with cytosolic pathways. We also identify important challenges that lie ahead, which need to be addressed for organelle engineering to become as mainstream as cytosolic engineering in academia and industry.

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Figure 1: Overview of yeast subcellular compartments.
Figure 2: Partial and complete metabolic pathways targeted to yeast mitochondria.
Figure 3: Compartmentalization of biosynthetic pathways in yeast peroxisomes.
Figure 4: Pathway localization to the yeast ER, Golgi and vacuoles.
Figure 5: Schemes harnessing the yeast cell wall for ethanol production from cellulosic biomass.

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Acknowledgements

J.L.A. is supported by grants from Princeton University and the Andlinger Center for Energy and the Environment, as well as by the Alfred P. Sloan Foundation. S.K.H. is supported by the NSF Graduate Research Fellowship Program (grant #DGE-1656466).

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  1. Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, USA

    Sarah K Hammer & José L Avalos

  2. Andlinger Center for Energy and the Environment, Princeton University, Princeton, New Jersey, USA

    José L Avalos

  3. Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA

    José L Avalos

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Correspondence to José L Avalos.

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Hammer, S., Avalos, J. Harnessing yeast organelles for metabolic engineering. Nat Chem Biol 13, 823–832 (2017). https://doi.org/10.1038/nchembio.2429

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