РЕКОМБИНАНТНЫЕ ШТАММЫ SACCHAROMYCES CEREVISIAE ДЛЯ ПОЛУЧЕНИЯ ЭТАНОЛА ИЗ РАСТИТЕЛЬНОЙ БИОМАССЫ

Saccharomyces cerevisiae является наиболее подходящим и используемым организмом для промышленного получения биоэтанола из сахаров, так как дрожжи имеют высокие темпы роста, ферментации и наработки этанола в анаэробных условиях, а также они устойчивы к высоким концентрациям этанола и низким значениям pH. Наиболее перспективным источником сахаров считается лигноцеллюлозная биомасса. Сахара, полученные из лигноцеллюлозной биомассы, являются смесью гексоз и пентоз. Однако используемые штаммы S. cerevisiae слабо приспособлены к сбраживанию пентасахаридов, в связи с чем необходима оптимизация метаболизма существующих в настоящее время продуцентов биоэтанола, направленная на использование пентасахаров. В работе представлен обзор существующих в мире подходов, разработанных для решения этой задачи с помощью рекомбинантных штаммов S. cerevisiae.

1. Ahmed S., Riaz S., Jamil A. Molecular cloning of fungal xylanases: an overview // Applied Microbiology Biotechnology. 2009. V. 84. No. 1. P. 19–35.

2. Almeida J.R., Modig T., Petersson A. et al. Increased tolerance and conversion of inhibitors in lignocellulosic hydrolysates by Saccharomyces cerevisiae // J. Chemical Technology biotechnology. 2007. V. 82. No. 4. P. 340–349.

3. Baek S.H., Kim S., Lee K. et al. Cellulosic ethanol production by combination of cellulase-displaying yeast cells // Enzyme Microbial Technology. 2012. V. 51. No. 6. P. 366–372.

4. Bera A., Ho N., Khan A., Sedlak M. A genetic overhaul of Saccharomyces cerevisiae 424A (LNH-ST) to improve xylose fermentation // J. industrial microbiology biotechnology. 2011. V. 38. No. 5. P. 617–626.

5. Çakar Z., Seker U., Tamerler C. et al. Evolutionary engineering of multiple-stress resistant Saccharomyces cerevisiae // FEMS yeast research. 2005. V. 5. No. 6-7. P. 569–578.

6. Çakar Z., Turanlı Y., Alkım C., Yılmaz Ü. Evolutionary engineering of Saccharomyces cerevisiae for improved industrially important properties // FEMS yeast research. 2012. V. 12. No. 2. P. 171–182.

7. Çelik E., Çalık P. Production of recombinant proteins by yeast cells // Biotechnology advances. 2012. V. 30. No. 5. P. 1108–1118.

8. Chen X., Meng K., Shi P. et al. High-level expression of a novel Penicillium endo-1, 3 (4)-β-d-glucanase with high specific activity in Pichia pastoris // J. industrial microbiology biotechnology. 2012. V. 39. No. 6. P. 869–876.

9. Cho K.M., Yoo Y.J., Kang H.S. δ-Integration of endo/exoglucanase and β-glucosidase genes into the yeast chromosomes for direct conversion of cellulose to ethanol // Enzyme Microbial Technology. 1999. V. 25. No. 1. P. 23–30.

10. De Figueiredo V., de Mello V., Reis V. et al. Functional expression of Burkholderia cenocepacia xylose isomerase in yeast increases ethanol production from a glucose–xylose blend // Bioresource Technology. 2013. V. 128. P. 792–796.

11. Deng X., Ho N. Xylulokinase activity in various yeasts including Saccharomyces cerevisiae containing the cloned xylulokinase gene // Applied Biochemistry Biotechnology. 1990. V. 24. No. 1. P. 193–199.

12. Fiaux J., ъakar Z.P ., Sonderegger M. et al. Metabolic-flux profi ling of the yeasts Saccharomyces cerevisiae and Pichia stipitis // Eukaryotic cell. 2003. V. 2. No. 1. P. 170–180.

13. Fujii T., Yu G., Matsushika A. et al. Ethanol production from xylo-oligosaccharides by xylose-fermenting Saccharomyces cerevisiae expressing β-xylosidase // Bioscience, biotechnology, biochemistry. 2011. V. 75. No. 6. P. 1140–1146.

14. Geddes C.C., Nieves I.U., Ingram L.O. Advances in ethanol production // Current opinion biotechnology. 2011. V. 22. No. 3. P. 312–319.

15. Goyal G., Tsai S.L., Madan B. et al. Simultaneous cell growth and ethanol production from cellulose by an engineered yeast consortium displaying a functional mini-cellulosome // Microb. Cell Fact. 2011. V. 10. P. 89.

16. Gurgu L., Lafraya А., Polaina, J., Marín-Navarro J. Fermentation of cellobiose to ethanol by industrial Saccharomyces strains carrying the β-glucosidase gene (BGL 1) from Saccharomycopsis fi buligera // Bioresource technology. 2011. V. 102. No. 8. P. 5229–5236.

17. Hector R.E., Qureshi N., Hughes S. et al. Expression of a heterologous xylose transporter in a Saccharomyces cerevisiae strain engineered to utilize xylose improves aerobic xylose consumption // Applied microbiology biotechnology. 2008. V. 80. No. 4. P. 675–684.

18. Ilmén M., Den Haan R., Brevnova E. et al. High level secretion of cellobiohydrolases by Saccharomyces cerevisiae // Biotechnol Biofuels. 2011. V. 4. P. 30.

19. Inokuma K., Hasunuma T., Kondo A. Effi cient yeast cellsurface display of exo-and endo-cellulase using the SED1 anchoring region and its original promoter // Biotechnology biofuels. 2014. V. 7. No. 1. P. 8.

20. Jayaram V., Cuyvers S., Verstrepen K. et al. Succinic acid in levels produced by yeast (Saccharomyces cerevisiae) during fermentation strongly impacts wheat bread dough properties // Food chemistry. 2014. V. 151. P. 421–428.

21. Karaoglan M., Yildiz H., Inan M. Screening of signal sequences for extracellular production of Aspergillus niger xylanase in Pichia pastoris // Biochemical Engineering J. 2014.

22. Katahira S., Fujita Y., Mizuike A. et al. Construction of a xylanfermenting yeast strain through codisplay of xylanolytic enzymes on the surface of xylose-utilizing Saccharomyces cerevisiae cells // Applied Environmental Microbiology. 2004. V. 70. No. 9. P. 5407–5414.

23. Katahira S., Ito M., Takema H. et al. Improvement of ethanol productivity during xylose and glucose co-fermentation by xylose-assimilating S. cerevisiae via expression of glucose transporter Sut1 // Enzyme Microbial Technology. 2008. V. 43. No. 2. P. 115–119.

24. Khattab S., Saimura M., Kodaki T. Boost in bioethanol production using recombinant Saccharomyces cerevisiae with mutated strictly NADPH-dependent xylose reductase and NADP-dependent xylitol dehydrogenase // J. biotechnology. 2013. V. 165. No. 3. P. 153–156.

25. Kim S., Skerker J.M., Kang W. et al. Rational and evolutionary engineering approaches uncover a small set of genetic changes efficient for rapid xylose fermentation in Saccharomyces cerevisiae // PloS one. 2013a. V. 8. No. 2. P. e57048.

26. Kim S., Lee K., Kong I. et al. Construction of an efficient xylose-fermenting diploid Saccharomyces cerevisiae strain through mating of two engineered haploid strains capable of xylose assimilation // J. Biotechnology. 2013b. V. 164. No. 1. P. 105–111.

27. Kirikyali N., Connerton I.F. Heterologous expression and kinetic characterisation of Neurospora crassa β-xylosidase in Pichia pastoris // Enzyme microbial technology. 2014. V. 57. P. 63–68.

28. Kitagawa T., Kohda K., Tokuhiro K. et al. Identifi cation of genes that enhance cellulase protein production in yeast // J. biotechnology. 2011. V. 151. No. 2. P. 194–203.

29. Kötter P., Ciriacy M. Xylose fermentation by Saccharomyces cerevisiae // Applied microbiology and biotechnology. 1993. V. 38. No. 6. P. 776–783.

30. Kötter P., Amore R., Hollenberg C.P., Ciriacy M. Isolation and characterization of the Pichia stipitis xylitol dehydrogenase gene, XYL2, and construction of a xyloseutilizing Saccharomyces cerevisiae transformant // Current genetics. 1990. V. 18. No. 6. P. 493–500.

31. Kruckeberg A.L. The hexose transporter family of Saccharomyces cerevisiae // Archives microbiology. 1996. V. 166. No. 5. P. 283–292.

32. Kuyper M., Harhangi, H.R., Stave A. et al. High level functional expression of a fungal xylose isomerase: the key to effi cient ethanolic fermentation of xylose by Saccharomyces cerevisiae? // FEMS Yeast Research. 2003. V. 4. No. 1. P. 69–78.

33. Kuyper M., Hartog M., Toirkens M. et al. Metabolic engineering of a xylose isomerase expressing Saccharomyces cerevisiae strain for rapid anaerobic xylose fermentation // FEMS Yeast Research. 2005a. V. 5. No. 4-5. P. 399–409.

34. Kuyper M., Toirkens M., Diderich J. et al. Evolutionary engineering of mixed-sugar utilization by a xylose- fermenting Saccharomyces cerevisiae strain // FEMS Yeast Research. 2005b. V. 5. No. 10. P. 925–934.

35. Kuyper M., Winkler A., Dijken J., Pronk J. Minimal metabolic engineering of Saccharomyces cerevisiae for efficient anaerobic xylose fermentation: a proof of principle // FEMS yeast research. 2004. V. 4. No. 6. P. 655–664.

36. Lee S., Kodaki T., Park Y. et al. Effects of NADH-preferring xylose reductase expression on ethanol production from xylose in xylose-metabolizing recombinant Saccharomyces cerevisiae // J. Biotechnology. 2012. V. 158.

37. Lin Y., Tanaka S. Ethanol fermentation from biomass resources: current state and prospects // Applied microbiology biotechnology. 2006. V. 69. No. 6. P. 627–642.

38. Liu E., Hu Y. Construction of a xylose-fermenting Saccharomyces cerevisiae strain by combined approaches of genetic engineering, chemical mutagenesis and evolutionary adaptation // Biochemical Engineering J. 2010. V. 48. No. 2. P. 204–210.

39. Lu C., Jeffries T. Shuffl ing of promoters for multiple genes to optimize xylose fermentation in an engineered Saccharomyces cerevisiae strain // Applied environmental microbiology. 2007. V. 73. No. 19. P. 6072–6077.

40. Madhavan A., Tamalampudi S., Ushida K. et al. Xylose isomerase from polycentric fungus Orpinomyces: gene sequencing, cloning, and expression in Saccharomyces cerevisiae for bioconversion of xylose to ethanol // Applied microbiology biotechnology. 2009. V. 82. No. 6. P. 1067–1078.

41. Matano Y., Hasunuma T., Kondo A. Display of cellulases on the cell surface of Saccharomyces cerevisiae for high yield ethanol production from high-solid lignocellulosic biomass // Bioresource technology. 2012. V. 108. P. 128–133.

42. Matsushika A., Inoue H., Kodaki T., Sawayama S. Ethanol production from xylose in engineered Saccharomyces cerevisiae strains: current state and perspectives // Applied Microbiology Biotechnology. 2009. V. 84. No. 1. P. 37–53.

43. Mimitsuka T., Sawai K., Kobayashi K. et al. Production of dlactic acid in a continuous membrane integrated fermentation reactor by genetically modified Saccharomyces cerevisiae: Enhancement in d-lactic acid carbon yield // J. bioscience bioengineering. 2014.

44. Mormeneo M., Pastor F., Zueco J. Efficient expression of a Paenibacillus barcinonensis endoglucanase in Saccharomyces cerevisiae // J. industrial microbiology biotechnology. 2012. V. 39. No. 1. P. 115–123.

45. Nakatani Y., Yamada R., Ogino C., Kondo A. Synergetic effect of yeast cell-surface expression of cellulase and expansinlike protein on direct ethanol production from cellulose // Microb. Cell Fact. 2013. V. 12. P. 66.

46. Ojeda K., Sánchez E., El-Halwagi M., Kafarov V. Exergy analysis and process integration of bioethanol production from acid pre-treated biomass: comparison of SHF, SSF and SSCF pathways // Chemical Engineering J. 2011. V. 176. P. 195–201.

47. Ota M., Sakuragi H., Morisaka H. et al. Display of Clostridium cellulovorans xylose isomerase on the cell surface of Saccharomyces cerevisiae and its direct application to xylose fermentation // Biotechnology Progress. 2013. V. 29. No. 2. P. 346–351.

48. Runquist D., Hahn-Hagerdal B., Radstrom P. Comparison of heterologous xylose transporters in recombinant Saccharomyces cerevisiae // Biotechnol Biofuels. 2010. V. 3. No. 5.

49. Runquist D., Fonseca C., Rаdstrцm P. et al. Expression of the Gxf1 transporter from Candida intermedia improves fermentation performance in recombinant xylose-utilizing Saccharomyces cerevisiae // Applied Microbiology Biotechnology. 2009. V. 82. No. 1. P. 123–130.

50. Salusjärvi L., Kaunisto S., Holmström S. et al. Overexpression of NADH-dependent fumarate reductase improves Dxylose fermentation in recombinant Saccharomyces cerevisiae // J. industrial microbiology biotechnology. 2013. V. 40. No. 12. P. 1383–1392.

51. Sauer U. Evolutionary engineering of industrially important microbial phenotypes // Metabolic Engineering. Springer Berlin Heidelberg, 2001. P. 129–169.

52. Sonderegger M., Sauer U. Evolutionary engineering of Saccharomyces cerevisiae for anaerobic growth on xylose // Applied and environmental microbiology. 2003. V. 69. No. 4. P. 1990–1998.

53. Steen E.J., Chan R., Prasad N. et al. Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol // Microb. Cell Fact. 2008. V. 7. No. 1. P. 36.

54. Sun J., Wen F., Si T. et al. Direct conversion of xylan to ethanol by recombinant Saccharomyces cerevisiae strains displaying an engineered minihemicellulosome // Applied environmental microbiology. 2012. V. 78. No. 11. P. 3837–3845.

55. Suzuki H., Imaeda T., Kitagawa T., Kohda K. Deglycosylation of cellulosomal enzyme enhances cellulosome assembly in Saccharomyces cerevisiae // J. Biotechnology. 2012. V. 157. No. 1. P. 64–70.

56. Van Wyk N., Den Haan R., Van Zyl W.H. Heterologous co-production of Thermobifi da fusca Cel9A with other cellulases in Saccharomyces cerevisiae // Applied microbiology biotechnology. 2010. V. 87. No. 5. P. 1813–1820.

57. Walfridsson M., Bao X., Anderlund M. et al. Ethanolic fermentation of xylose with Saccharomyces cerevisiae harboring the Thermus thermophilus xylA gene, which expresses an active xylose (glucose) isomerase // Applied environmental microbiology. 1996. V. 62. No. 12. P. 4648–4654.

58. Wang P., Schneider H. Growth of yeasts on D-xylulose // Canadian J. microbiology. 1980. V. 26. No. 9. P. 1165– 1168.

59. Wang T.Y., Huang, C.J., Chen H.L. et al. Systematic screening of glycosylation-and traffi cking-associated gene knockouts in Saccharomyces cerevisiae identifies mutants with improved heterologous exocellulase activity and host secretion // BMC biotechnology. 2013. V. 13. No. 1. P. 71.

60. Wilde C., Gold N.D., Bawa N. et al. Expression of a library of fungal β-glucosidases in Saccharomyces cerevisiae for the development of a biomass fermenting strain // Applied microbiology biotechnology. 2012. V. 95. No. 3. P. 647–659.

61. Xu L., Shen Y., Hou J. et al. Promotion of Extracellular Activity of Cellobiohydrolase I from Trichoderma reesei by Protein Glycosylation Engineering in Saccharomyces cerevisiae // Curr Synthetic Sys Biol. 2014. V. 2. No. 111. P. 2332–0737.1000111.

62. Yamada R., Taniguchi N., Tanaka T. et al. Direct ethanol production from cellulosic materials using a diploid strain of Saccharomyces cerevisiae with optimized cellulase expression // Biotechnol Biofuels. 2011. V. 4. No. 8.

63. Young E.M., Tong A., Bui H. et al. Rewiring yeast sugar transporter preference through modifying a conserved protein motif // Proc. Natl Academy Sciences. 2014. V. 111. No. 1. P. 131–136.

64. Yu J., Singh D., Liu N. et al. Construction of a Glucose and Xylose Co-Fermenting Industrial Saccharomyces cerevisiae by Expression of Codon-Optimized Fungal Xylose Isomerase // J. Biobased Materials Bioenergy. 2011. V. 5. No. 3. P. 357–364.

65. Zhou H., Cheng J.S., Wang B.L. et al. Xylose isomerase overexpression along with engineering of the pentose phosphate pathway and evolutionary engineering enable rapid xylose utilization and ethanol production by Saccharomyces cerevisiae // Metabolic engineering. 2012. V. 14. No. 6. P. 611–622.