Article | Published:

An artificial transport metabolon facilitates improved substrate utilization in yeast

Nature Chemical Biology volume 13, pages 11581163 (2017) | Download Citation

Abstract

Efficient substrate utilization is the first and most important prerequisite for economically viable production of biofuels and chemicals by microbial cell factories. However, production rates and yields are often compromised by low transport rates of substrates across biological membranes and their diversion to competing pathways. This is especially true when common chassis organisms are engineered to utilize nonphysiological feedstocks. Here, we addressed this problem by constructing an artificial complex between an endogenous sugar transporter and a heterologous xylose isomerase in Saccharomyces cerevisiae. Direct feeding of the enzyme through the transporter resulted in acceleration of xylose consumption and substantially diminished production of xylitol as an undesired side product, with a concomitant increase in the production of ethanol. This underlying principle could also likely be implemented in other biotechnological applications.

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Acknowledgements

Financial support by German Federal Ministry of Food, Agriculture and Consumer Protection following a decision of German Bundestag (to E.B. and M.O.; project ECO-FERM, FKZ: 22031811) is gratefully acknowledged. We would like to thank D. Wolf (University of Stuttgart) for kindly providing Gal2 antibodies. We are grateful to C. Hiesl, C. Hannig and S. Scholl for their contribution to the experimental work. We thank J. Tripp and W. Generoso for stimulating discussions. T. Bionda is acknowledged for critical comments on the manuscript.

Author information

Author notes

    • Thomas Thomik

    Present address: Rentschler Biotechnologie, Laupheim, Germany.

Affiliations

  1. Institute of Molecular Biosciences, Goethe University, Frankfurt am Main, Germany.

    • Thomas Thomik
    • , Eckhard Boles
    •  & Mislav Oreb
  2. Molecular Bioenergetics, Center of Biological Chemistry, Cluster of Excellence Frankfurt Macromolecular Complexes, Goethe University, Frankfurt, Germany.

    • Ilka Wittig
  3. Functional Proteomics, Institute of Biochemistry I, Faculty of Medicine, Goethe University, Frankfurt, Germany.

    • Ilka Wittig
  4. Department of Biochemistry and Molecular Biology, Chicago Medical School, Rosalind Franklin University, North Chicago, Illinois, USA.

    • Jun-yong Choe

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Contributions

M.O. conceived and supervised the project. E.B. co-supervised the project and provided resources. T.T., I.W., E.B. and M.O. contributed to experimental design. T.T. performed the experiments. T.T. and M.O. analyzed the data. J.C. performed structure modeling. M.O. wrote the manuscript, which was edited and approved by all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Mislav Oreb.

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    Supplementary Results, Supplementary Tables 1 and 2, and Supplementary Figures 1–8

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DOI

https://doi.org/10.1038/nchembio.2457