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Evaluating the Engineered Saccharomyces cerevisiae With High Spermidine Contents for Increased Tolerance to Lactic, Succinic, and Malic Acids and Increased Xylose Fermentation

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Abstract

Saccharomyces cerevisiae is a promising candidate for production of organic acids as it is more tolerant to these acids than the prokaryotes. However, the large-scale production of organic acids from lignocellulosic biomass is limited by their accumulation in the growth medium and inability of xylose fermentation by S. cerevisiae. Here we showed that high intracellular spermidine (SPD) contents confers enhanced tolerance to lactic, succinic, and malic acids in S. cerevisiae. Specifically, in the presence of 20 g/L malic acid, the maximum specific growth rate and dry cell weight of a S. cerevisiae with two fold higher SPD content were 40% and 36% higher than those of the control strain. When a xylose assimilation pathway was introduced into an engineered strain with high SPD content, the resulting S. cerevisiae strain exhibited 23∼47% higher xylose consumption rate and 6∼16% higher ethanol productivity than those of the control strain during the four times of repeated-batch fermentations using a mixture of glucose and xylose as carbon sources. These results suggest that the strain developed in this study would serve as a platform strain for production of organic acids.

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References

  1. Es, I., A. M. Khaneghah, F. J. Barba, J. A. Saraiva, A. S. Sant’Ana, and S. M. B. Hashemi (2018) Recent advancements in lactic acid production - a review. Food Res. Int. 107: 763–770.

    Article  CAS  Google Scholar 

  2. Akhtar, J., A. Idris, and R. Abd Aziz (2014) Recent advances in production of succinic acid from lignocellulosic biomass. Appl. Microbiol. Biotechnol. 98: 987–1000.

    Article  CAS  Google Scholar 

  3. Mienda, B. S. and F. M. Salleh (2017) Bio-succinic acid production: Escherichia coli strains design from genome-scale perspectives. Aims Bioeng. 4: 418–430.

    Article  CAS  Google Scholar 

  4. Heo, W., J. H. Kim, S. Kim, K. H. Kim, H. J. Kim, and J. H. Seo (2019) Enhanced production of 3-hydroxypropionic acid from glucose and xylose by alleviation of metabolic congestion due to glycerol flux in engineered Escherichia coli. Bioresour. Technol. 285: 121320.

    Article  CAS  Google Scholar 

  5. Lee, Y., O. Nasution, Y. M. Lee, E. Kim, W. Choi, and W. Kim (2017) Overexpression of PMA1 enhances tolerance to various types of stress and constitutively activates the SAPK pathways in Saccharomyces cerevisiae. Appl. Microbiol. Biotechnol. 101: 229–239.

    Article  CAS  Google Scholar 

  6. Hasunuma, T., T. Sanda, R. Yamada, K. Yoshimura, J. Ishii, and A. Kondo (2011) Metabolic pathway engineering based on metabolomics confers acetic and formic acid tolerance to a recombinant xylose-fermenting strain of Saccharomyces cerevisiae. Microb. Cell Fact. 10: 2.

    Article  CAS  Google Scholar 

  7. Mira, N. P., M. C. Teixeira, and I. Sa-Correia (2010) Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: a genome-wide view. OMICS. 14: 525–540.

    Article  CAS  Google Scholar 

  8. Baek, S. H., E. Y. Kwon, S. Y. Kim, and J. S. Hahn (2016) GSF2 deletion increases lactic acid production by alleviating glucose repression in Saccharomyces cerevisiae. Sci. Rep. 6: 34812.

    Article  CAS  Google Scholar 

  9. Eraso, P. and C. Gancedo (1987) Activation of yeast plasma membrane ATPase by acid pH during growth. FEBS Lett. 224: 187–192.

    Article  CAS  Google Scholar 

  10. Pampulha, M. E. and M. C. Loureiro-Dias (1990) Activity of glycolytic enzymes of Saccharomyces cerevisiae in the presence of acetic acid. Appl. Microbiol. Biotechnol. 34: 375–380.

    Article  CAS  Google Scholar 

  11. Branduardi, P., M. Sauer, L. De Gioia, G. Zampella, M. Valli, D. Mattanovich, and D. Porro (2006) Lactate production yield from engineered yeasts is dependent from the host background, the lactate dehydrogenase source and the lactate export. Microb. Cell Fact. 5: 4.

    Article  Google Scholar 

  12. Kim, S. K., Y. S. Jin, I. G. Choi, Y. C. Park, and J. H. Seo (2015) Enhanced tolerance of Saccharomyces cerevisiae to multiple lignocellulose-derived inhibitors through modulation of spermidine contents. Metab. Eng. 29: 46–55.

    Article  CAS  Google Scholar 

  13. Balasundaram, D., C. W. Tabor, and H. Tabor (1993) Oxygen toxicity in a polyamine-depleted spe2Δ mutant of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA. 90: 4693–4697.

    Article  CAS  Google Scholar 

  14. Eisenberg, T., H. Knauer, A. Schauer, S. Buttner, C. Ruckenstuhl, D. Carmona-Gutierrez, J. Ring, S. Schroeder, C. Magnes, L. Antonacci, H. Fussi, L. Deszcz, R. Hartl, E. Schraml, A. Criollo, E. Megalou, D. Weiskopf, P. Laun, G. Heeren, M. Breitenbach, B. Grubeck-Loebenstein, E. Herker, B. Fahrenkrog, K. U. Frohlich, F. Sinner, N. Tavernarakis, N. Minois, G. Kroemer, and F. Madeo (2009) Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11: 1305–1314.

    Article  CAS  Google Scholar 

  15. Stanley, D., A. Bandara, S. Fraser, P. J. Chambers, and G. A. Stanley (2010) The ethanol stress response and ethanol tolerance of Saccharomyces cerevisiae. J. Appl. Microbiol. 109: 13–24.

    CAS  PubMed  Google Scholar 

  16. Kwak, S., J. H. Jo, E. J. Yun, Y. S. Jin, and J. H. Seo (2019) Production of biofuels and chemicals from xylose using native and engineered yeast strains. Biotechnol. Adv. 37: 271–283.

    Article  CAS  Google Scholar 

  17. Turner, T. L., G. C. Zhang, S. R. Kim, V. Subramaniam, D. Steffen, C. D. Skory, J. Y. Jang, B. J. Yu, and Y. S. Jin (2015) Lactic acid production from xylose by engineered Saccharomyces cerevisiae without PDC or ADH deletion. Appl. Microbiol. Biotechnol. 99: 8023–8033.

    Article  CAS  Google Scholar 

  18. Kim, S. K., J. H. Jo, Y. C. Park, Y. S. Jin, and J. H. Seo (2017) Metabolic engineering of Saccharomyces cerevisiae for production of spermidine under optimal culture conditions. Enzyme Microb. Technol. 101: 30–35.

    Article  CAS  Google Scholar 

  19. Hosaka, K., J. Nikawa, T. Kodaki, and S. Yamashita (1992) A dominant mutation that alters the regulation of Ino1 expression in Saccharomyces cerevisiae. J. Biochem. 111: 352–358.

    Article  CAS  Google Scholar 

  20. Kim, S. K., J. H. Jo, Y. S. Jin, and J. H. Seo (2017) Enhanced ethanol fermentation by engineered Saccharomyces cerevisiae strains with high spermidine contents. Bioprocess Biosyst. Eng. 40: 683–691.

    Article  CAS  Google Scholar 

  21. Wickerham, L. J. (1946) A critical evaluation of the nitrogen assimilation tests commonly used in the classification of yeasts. J. Bacteriol. 52: 293–301.

    Article  CAS  Google Scholar 

  22. Jo, J. H., Y. C. Park, Y. S. Jin, and J. H. Seo (2017) Construction of efficient xylose-fermenting Saccharomyces cerevisiae through a synthetic isozyme system of xylose reductase from Scheffersomyces stipitis. Bioresour. Technol. 241: 88–94.

    Article  CAS  Google Scholar 

  23. Abbott, D. A., R. M. Zelle, J. T. Pronk, and A. J. A. van Maris (2009) Metabolic engineering of Saccharomyces cerevisiae for production of carboxylic acids: current status and challenges. FEMS Yeast Res. 9: 1123–1136.

    Article  CAS  Google Scholar 

  24. Uemura, T., K. Kashiwagi, and K. Igarashi (2007) Polyamine uptake by DUR3 and SAM3 in Saccharomyces cerevisiae. J. Biol. Chem. 282: 7733–7741.

    Article  CAS  Google Scholar 

  25. Palanimurugan, R., H. Scheel, K. Hofmann, and R. J. Dohmen (2004) Polyamines regulate their synthesis by inducing expression and blocking degradation of ODC antizyme. EMBO J. 23: 4857–4867.

    Article  CAS  Google Scholar 

  26. Zelle, R. M., E. de Hulster, W. A. van Winden, P. de Waard, C. Dijkema, A. A. Winkler, J. M. A. Geertman, J. P. van Dijken, J. T. Pronk, and A. J. A. van Maris (2008) Malic acid production by Saccharomyces cerevisiae: Engineering of pyruvate carboxylation, oxaloacetate reduction, and malate export. Appl. Microbiol. Biotechnol. 74: 2766–2777.

    CAS  Google Scholar 

  27. McKinlay, J. B., C. Vieille, and J. G. Zeikus (2007) Prospects for a bio-based succinate industry. Appl. Microbiol. Biotechnol. 76: 727–740.

    Article  CAS  Google Scholar 

  28. Werpy, T. and G. Petersen (2004) Top value added chemicals from biomass: Volume I: results of screening for potential candidates from sugars and synthesis gas. Technical report, U.S. Department of Energy, Oak Ridge, TN, USA.

    Google Scholar 

  29. Abbott, D. A., T. A. Knijnenburg, L. M. I. de Poorter, M. J. T. Reinders, J. T. Pronk, and A. J. A. van Maris (2007) Generic and specific transcriptional responses to different weak organic acids in anaerobic chemostat cultures of Saccharomyces cerevisiae. FEMS Yeast Res. 7: 819–833.

    Article  CAS  Google Scholar 

  30. Mira, N. P., A. B. Lourenco, A. R. Fernandes, J. D. Becker, and I. Sa-Correia (2009) The RIM101 pathway has a role in Saccharomyces cerevisiae adaptive response and resistance to propionic acid and other weak acids. FEMS Yeast Res. 9: 202–216.

    Article  CAS  Google Scholar 

  31. Kim, S. R., K. S. Lee, J. H. Choi, S. J. Ha, D. H. Kweon, J. H. Seo, and Y. S. Jin (2010) Repeated-batch fermentations of xylose and glucose-xylose mixtures using a respiration-deficient Saccharomyces cerevisiae engineered for xylose metabolism. J. Biotechnol. 150: 404–407.

    Article  CAS  Google Scholar 

  32. Zhang, J. and R. Greasham (1999) Chemically defined media for commercial fermentations. Appl. Microbiol. Biotechnol. 51: 407–421.

    Article  CAS  Google Scholar 

  33. Kim, S. R., J. M. Skerker, W. Kang, A. Lesmana, N. Wei, A. P. Arkin, and Y. S. Jin (2013) Rational and evolutionary engineering approaches uncover a small set of genetic changes efficient for rapid xylose fermentation in Saccharomyces cerevisiae. PLos One. 8: e57048.

    Article  CAS  Google Scholar 

  34. Kim, S. R., Y. C. Park, Y. S. Jin, and J. H. Seo (2013) Strain engineering of Saccharomyces cerevisiae for enhanced xylose metabolism. Biotechnol. Adv. 31: 851–861.

    Article  CAS  Google Scholar 

  35. Ha, S. J., J. M. Galazka, S. R. Kim, J. H. Choi, X. Yang, J. H. Seo, N. L. Glass, J. H. D. Cate, and Y. S. Jin (2011) Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose fermentation. Proc. Natl. Acad. Sci. USA. 108: 504–509.

    Article  CAS  Google Scholar 

  36. Gopinarayanan, V. E. and N. U. Nair (2018) A semi-synthetic regulon enables rapid growth of yeast on xylose. Nat. Commun. 9: 1233.

    Article  Google Scholar 

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Acknowledgements

This work was financially supported by the National Research Foundation of Korea (NRF) Grant (2019R1C 1C1003521) funded by the Korean Ministry of Science, ICT and Future Planning.

The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

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  1. Department of Food Science and Technology, Chung-Ang University, Anseong, 17546, Korea

    Sun-Ki Kim & Joong-Hyuck Auh

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  1. Sun-Ki Kim
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Correspondence to Sun-Ki Kim or Joong-Hyuck Auh.

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Kim, SK., Auh, JH. Evaluating the Engineered Saccharomyces cerevisiae With High Spermidine Contents for Increased Tolerance to Lactic, Succinic, and Malic Acids and Increased Xylose Fermentation. Biotechnol Bioproc E 26, 47–54 (2021). https://doi.org/10.1007/s12257-020-0020-y

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