Abstract
The search for gasoline substitutes has grown in recent decades, leading to the increased production of ethanol as viable alternative. However, research in recent years has shown that butanol exhibits various advantages over ethanol as a biofuel. Furthermore, butanol can also be used as a chemical platform, serving as an intermediate product and as a solvent in industrial reactions. This alcohol is naturally produced by some Clostridium species; however, Clostridial fermentation processes still have inherent problems, which focuses the interest on Saccharomyces cerevisiae for butanol production, as an alternative organism for the production of this alcohol. S. cerevisiae exhibits great adaptability to industrial conditions and can be modified with a wide range of genetic tools. Although S. cerevisiae is known to naturally produce isobutanol, the n-butanol synthesis pathway has not been well established in wild S. cerevisiae strains. Two strategies are most commonly used for of S. cerevisiae butanol production: the heterologous expression of the Clostridium pathway or the amino acid uptake pathways. However, butanol yields produced from S. cerevisiae are lower than ethanol yield. Thus, there are still many challenges needed to be overcome, which can be minimized through genetic and evolutive engineering, for butanol production by yeast to become a reality.
Similar content being viewed by others
References
Amiri H, Karimi K (2019) Biobutanol production. in: advanced bioprocessing for alternative fuels, biobased chemicals, and bioproducts (Ed. Majid Hosseini). Elsevier, Woodhead, https://doi.org/10.1016/C2018-0-02436-6
Atsumi S, Cann AF, Connor MR et al (2008) Metabolic engineering of Escherichia coli for 1-butanol production. Metab Eng 10:305–311. https://doi.org/10.1016/j.ymben.2007.08.003
Beato FB, Bergdahl B, Rosa CA et al (2016) Physiology of Saccharomyces cerevisiae strains isolated from Brazilian biomes: New insights into biodiversity and industrial applications. FEMS Yeast Res 16:1–14. https://doi.org/10.1093/femsyr/fow076
Branduardi P, Longo V, Berterame NM et al (2013) A novel pathway to produce butanol and isobutanol in Saccharomyces cerevisiae. Biotechnol Biofuels 6:68. https://doi.org/10.1186/1754-6834-6-68
Brethauer S, Studer MH (2015) Biochemical conversion processes of lignocellulosic biomass to fuels and chemicals—a review. Chimia (Aarau) 69:572–581. https://doi.org/10.2533/chimia.2015.572
Chen CT, Liao JC (2016) Frontiers in microbial 1-butanol and isobutanol production. FEMS Microbiol Lett 363:1–13. https://doi.org/10.1093/femsle/fnw020
Chen T, Xu F, Zhang W et al (2019) High butanol production from glycerol by using Clostridium sp. strain CT7 integrated with membrane assisted pervaporation. Bioresour Technol. https://doi.org/10.1016/j.biortech.2019.121530
Cheng C, Bao T, Yang S-T (2019) Engineering Clostridium for improved solvent production: recent progress and perspective. Appl Microbiol Biotechnol 103:5549–5566. https://doi.org/10.1007/s00253-019-09916-7
Choi YJ, Lee J, Jang Y, Lee SY (2014) Metabolic engineering of microorganisms for the production of higher alcohols. MBio 5:1–10. https://doi.org/10.1128/mBio.01524-14.Copyright
Crook N, Sun J, Morse N et al (2016) Identification of gene knockdown targets conferring enhanced isobutanol and 1-butanol tolerance to Saccharomyces cerevisiae using a tunable RNAi screening approach. Appl Microbiol Biotechnol 100:10005–10018. https://doi.org/10.1007/s00253-016-7791-2
Della-Bianca BE, Gombert AK (2013) Stress tolerance and growth physiology of yeast strains from the Brazilian fuel ethanol industry. Antonie van Leeuwenhoek, Int J Gen Mol Microbiol 104:1083–1095. https://doi.org/10.1007/s10482-013-0030-2
Dürre P (2007) Biobutanol: An attractive biofuel. Biotechnol J 2:1525–1534. https://doi.org/10.1002/biot.200700168
Dürre P (2008) Fermentative butanol production: bulk chemical and biofuel. Ann NY Acad Sci 1125:353–362. https://doi.org/10.1196/annals.1419.009
Generoso WC, Schadeweg V, Oreb M, Boles E (2015) Metabolic engineering of Saccharomyces cerevisiae for production of butanol isomers. Curr Opin Biotechnol 33:1–7. https://doi.org/10.1016/j.copbio.2014.09.004
Ghiaci P, Norbeck J, Larsson C (2013) Physiological adaptations of Saccharomyces cerevisiae evolved for improved butanol tolerance. Biotechnol Biofuels 6:1–12. https://doi.org/10.1186/1754-6834-6-101
González-Ramos D, van den Broek M, van Maris A et al (2013) Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation. Biotechnol Biofuels 6:48. https://doi.org/10.1186/1754-6834-6-48
Gu Y, Jiang Y, Wu H et al (2011) Economical challenges to microbial producers of butanol: Feedstock, butanol ratio and titer. Biotechnol J 6:1348–1357. https://doi.org/10.1002/biot.201100046
Heap JT, Pennington OJ, Cartman ST et al (2007) The ClosTron: a universal gene knock-out system for the genus Clostridium. J Microbiol Methods. https://doi.org/10.1016/j.mimet.2007.05.021
Hong KK, Nielsen J (2012) Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries. Cell Mol Life Sci 69:2671–2690. https://doi.org/10.1007/s00018-012-0945-1
Hong ME, Lee KS, Yu BJ et al (2010) Identification of gene targets eliciting improved alcohol tolerance in Saccharomyces cerevisiae through inverse metabolic engineering. J Biotechnol 149:52–59. https://doi.org/10.1016/j.jbiotec.2010.06.006
Huang J, Du Y, Bao T et al (2019) Production of n-butanol from cassava bagasse hydrolysate by engineered Clostridium tyrobutyricum overexpressing adhE2: Kinetics and cost analysis. Bioresour Technol 292:121969. https://doi.org/10.1016/J.BIORTECH.2019.121969
Ishmayana S, Kennedy UJ, Learmonth RP (2017) Further investigation of relationships between membrane fluidity and ethanol tolerance in Saccharomyces cerevisiae. World J Microbiol Biotechnol 33:1–10. https://doi.org/10.1007/s11274-017-2380-9
Jiang Y, Liu J, Jiang W et al (2015) Current status and prospects of industrial bio-production of n-butanol in China. Biotechnol Adv 33:1493–1501. https://doi.org/10.1016/j.biotechadv.2014.10.007
Jones DT, Woods DR (1986) Acetone-butanol fermentation revisited. Microbiol Rev 50:484–524
Knoshaug EP, Zhang M (2009) Butanol tolerance in a selection of microorganisms. Appl Biochem Biotechnol 153:13–20. https://doi.org/10.1007/s12010-008-8460-4
Krivoruchko A, Serrano-Amatriain C, Chen Y et al (2013) Improving biobutanol production in engineered Saccharomyces cerevisiae by manipulation of acetyl-CoA metabolism. J Ind Microbiol Biotechnol 40:1051–1056. https://doi.org/10.1007/s10295-013-1296-0
Kuroda K, Ueda M (2015) Cellular and molecular engineering of yeast Saccharomyces cerevisiae for advanced biobutanol production. FEMS Microbiol Lett 363:1–24. https://doi.org/10.1093/femsle/fnv247
Kushwaha D, Srivastava N, Mishra I et al (2019) Recent trends in biobutanol production. Rev Chem Eng 35:475–504. https://doi.org/10.1515/revce-2017-0041
Lee SH, Kim S, Kim JY et al (2016) Enhanced butanol fermentation using metabolically engineered Clostridium acetobutylicum with ex situ recovery of butanol. Bioresour Technol 218:909–917. https://doi.org/10.1016/j.biortech.2016.07.060
Lee SY, Park JH, Jang SH et al (2008) Fermentative butanol production by clostridia. Biotechnol Bioeng 101(2):209–228
Lian J, Si T, Nair NU, Zhao H (2014) Design and construction of acetyl-CoA overproducing Saccharomyces cerevisiae strains. Food, Pharm Bioeng Div 2014—Core Program Area 2014 AIChE Annu Meet 2: 750–760.
Liu S, Qureshi N (2009) How microbes tolerate ethanol and butanol. N Biotechnol 26:117–121. https://doi.org/10.1016/j.nbt.2009.06.984
Mans R, Daran JMG, Pronk JT (2018) Under pressure: evolutionary engineering of yeast strains for improved performance in fuels and chemicals production. Curr Opin Biotechnol 50:47–56. https://doi.org/10.1016/j.copbio.2017.10.011
Ndaba B, Chiyanzu I, Marx S (2015) n-Butanol derived from biochemical and chemical routes: a review. Biotechnol Reports 8:1–9. https://doi.org/10.1016/j.btre.2015.08.001
Pereira FB, Guimarães PMR, Teixeira JA, Domingues L (2011) Robust industrial Saccharomyces cerevisiae strains for very high gravity bio-ethanol fermentations. J Biosci Bioeng 112:130–136. https://doi.org/10.1016/j.jbiosc.2011.03.022
Sakuragi H, Morisaka H, Kuroda K, Ueda M (2015) Enhanced butanol production by eukaryotic Saccharomyces cerevisiae engineered to contain an improved pathway. Biosci Biotechnol Biochem 79:314–320. https://doi.org/10.1080/09168451.2014.972330
Sauer M, Baral N, Slutzky L et al (2016) Industrial production of acetone and butanol by fermentation—100 years later. FEMS Microbiol Lett 363:1525–1534. https://doi.org/10.1093/femsle/fnw134
Schadeweg V, Boles E (2016a) n-Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl-CoA. Biotechnol Biofuels 9:44. https://doi.org/10.1186/s13068-016-0456-7
Schadeweg V, Boles E (2016b) Increasing n-butanol production with Saccharomyces cerevisiae by optimizing acetyl-CoA synthesis, NADH levels and trans-2-enoyl-CoA reductase expression. Biotechnol Biofuels 9:1–11. https://doi.org/10.1186/s13068-016-0673-0
Schiel-Bengelsdorf B, Montoya J, Linder S, Dürre P (2013) Butanol fermentation. Environ Technol (United Kingdom) 34:1691–1710. https://doi.org/10.1080/09593330.2013.827746
Shen CR, Liao JC (2008) Metabolic engineering of Escherichia coli for 1-butanol and 1-propanol production via the keto-acid pathways. Metab Eng 10:312–320. https://doi.org/10.1016/j.ymben.2008.08.001
Shi S, Si T, Liu Z et al (2016) Metabolic engineering of a synergistic pathway for n-butanol production in Saccharomyces cerevisiae. Sci Rep 6:25675. https://doi.org/10.1038/srep25675
Si T, Luo Y, Xiao H, Zhao H (2014) Utilizing an endogenous pathway for 1-butanol production in Saccharomyces cerevisiae. Metab Eng 22:60–68. https://doi.org/10.1016/j.ymben.2014.01.002
Steen EJ, Chan R, Prasad N et al (2008) Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol. Microb Cell Fact 7:1–8. https://doi.org/10.1186/1475-2859-7-36
Swidah R, Ogunlabi O, Grant CM, Ashe MP (2018) n-Butanol production in S. cerevisiae: co-ordinate use of endogenous and exogenous pathways. Appl Microbiol Biotechnol 102:9857–9866. https://doi.org/10.1007/s00253-018-9305-x
Swidah R, Wang H, Reid PJ et al (2015) Butanol production in S. cerevisiae via a synthetic ABE pathway is enhanced by specific metabolic engineering and butanol resistance. Biotechnol Biofuels. 8:97. 10.1186/s13068-015-0281-4
Teoh ST, Putri S, Mukai Y et al (2015) A metabolomics-based strategy for identification of gene targets for phenotype improvement and its application to 1-butanol tolerance in Saccharomyces cerevisiae. Biotechnol, Biofuels, p 8
Tracy BP, Gaida SM, Papoutsakis ET (2008) Development and application of flow-cytometric techniques for analyzing and sorting endospore-forming Clostridia. Appl Environ Microbiol 74(24):7497–7506. https://doi.org/10.1128/AEM.01626-08
Villas-Bôas SG, Åkesson M, Nielsen J (2005) Biosynthesis of glyoxylate from glycine in Saccharomyces cerevisiae. FEMS Yeast Res 5:703–709. https://doi.org/10.1016/j.femsyr.2005.03.001
Yüksel F, Yüksel B (2004) The use of ethanol–gasoline blend as a fuel in an SI engine. Renew Energy 29(7):1181–1191
Zhang Q, Yao M, Zheng Z, Liu H et al (2012) Experimental study of n-butanol addition on performance and emissions with diesel low temperature combustion. Energy 47(1):515–521
Acknowledgements
The authors thank the São Paulo State Research Foundation (FAPESP, Grants Nos. 2015/20630-4 and 2019/08542-3) for their financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoa de Nível Superior (CAPES, Brazil, Finance Code 001).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Azambuja, S.P.H., Goldbeck, R. Butanol production by Saccharomyces cerevisiae: perspectives, strategies and challenges. World J Microbiol Biotechnol 36, 48 (2020). https://doi.org/10.1007/s11274-020-02828-z
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11274-020-02828-z