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Enhanced production of para-hydroxybenzoic acid by genetically engineered Saccharomyces cerevisiae

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Abstract

Saccharomyces cerevisiae is a popular organism for metabolic engineering; however, studies aiming at over-production of bio-replacement precursors for the chemical industry often fail to overcome proof-of-concept stage. When intending to show real industrial attractiveness, the challenge is twofold: formation of the target compound must be increased, while minimizing the formation of side and by-products to maximize titer, rate and yield. To tackle these, the metabolism of the organism, as well as the parameters of the process, need to be optimized. Addressing both we show that S. cerevisiae is well-suited for over-production of aromatic compounds, which are valuable in chemical industry and are particularly useful in space technology. Specifically, a strain engineered to accumulate chorismate was optimized for formation of para-hydroxybenzoic acid. Then a fed-batch bioreactor process was developed, which delivered a final titer of 2.9 g/L, a maximum rate of 18.625 mgpHBA/(gCDW × h) and carbon-yields of up to 3.1 mgpHBA/gglucose.

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Notes

  1. At t = 36 h, when cells were becoming stationary, which was approx. 12 h after the end of exponential growth, the remaining 22.8 mL of culture were spiked with 5 mL medium that contained 200 g/L glucose.

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Acknowledgements

This study was funded by the Australian Research Council (DE120101549). We acknowledge the services of Metabolomics Australia for the analysis of metabolite concentrations, especially Dr. Manuel Plan. We also thank Dr. Gal Winter for support in the early stages of this work.

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Author notes

  1. Nils J. H. Averesch

    Present address: Universities Space Research Association at NASA Ames Research Center, Mountain View, CA, USA

  2. Alex Prima

    Present address: Department of Technical Biochemistry, Technical University of Dortmund, Dortmund, Germany

  3. Jens O. Krömer

    Present address: Department for Solar Materials, Helmholtz Centre for Environmental Research, Leipzig, Germany

Authors and Affiliations

  1. Centre for Microbial Electrochemical Systems (CEMES), The University of Queensland, Brisbane, Australia

    Nils J. H. Averesch, Alex Prima & Jens O. Krömer

  2. Advanced Water Management Centre (AWMC), The University of Queensland, Brisbane, Australia

    Nils J. H. Averesch, Alex Prima & Jens O. Krömer

Authors
  1. Nils J. H. Averesch
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  2. Alex Prima
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Correspondence to Nils J. H. Averesch.

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Averesch, N.J.H., Prima, A. & Krömer, J.O. Enhanced production of para-hydroxybenzoic acid by genetically engineered Saccharomyces cerevisiae . Bioprocess Biosyst Eng 40, 1283–1289 (2017). https://doi.org/10.1007/s00449-017-1785-z

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