Leveraging transcription factors to speed cellobiose fermentation by Saccharomyces cerevisiae

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• 作者：Yuping Lin (1)
  Kulika Chomvong (2)
  Ligia Acosta-Sampson (1)
  Ra铆ssa Estrela (1)
  Jonathan M Galazka (1)
  Soo Rin Kim (5) (6)
  Yong-Su Jin (5) (6)
  Jamie HD Cate (1) (3) (4)
  
  1. Departments of Molecular and Cell Biology ; University of California ; Berkeley ; CA ; 94720 ; USA
  2. Plant and Microbial Biology ; University of California ; Berkeley ; CA ; 94720 ; USA
  5. Department of Food Science and Human Nutrition ; University of Illinois at Urbana-Champaign ; Urbana ; Illinois ; 61801 ; USA
  6. Institute for Genomic Biology ; University of Illinois at Urbana-Champaign ; Urbana ; Illinois ; 61801 ; USA
  3. Chemistry ; University of California ; Berkeley ; CA ; 94720 ; USA
  4. Physical Biosciences Division ; Lawrence Berkeley National Laboratory ; Berkeley ; CA ; 94720 ; USA
  
• 关键词：Cellobiose ; Glycolysis ; Systems biology ; Transcription factor ; Metabolic engineering ; Biofuels
• 刊名：Biotechnology for Biofuels
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：2,101 KB
• 参考文献：1. Coulier, L, Zha, Y, Bas, R, Punt, PJ (2013) Analysis of oligosaccharides in lignocellulosic biomass hydrolysates by high-performance anion-exchange chromatography coupled with mass spectrometry (HPAEC-MS). Bioresour Technol 133: pp. 221-231 CrossRef
  2. Kim, SR, Ha, SJ, Wei, N, Oh, EJ, Jin, YS (2012) Simultaneous co-fermentation of mixed sugars: a promising strategy for producing cellulosic ethanol. Trends Biotechnol 30: pp. 274-282 CrossRef
  3. Hong, KK, Nielsen, J (2012) Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries. Cell Mol Life Sci 69: pp. 2671-2690 45-1" target="_blank" title="It opens in new window">CrossRef
  4. Dellomonaco, C, Fava, F, Gonzalez, R (2010) The path to next generation biofuels: successes and challenges in the era of synthetic biology. Microb Cell Factories 9: pp. 3 475-2859-9-3" target="_blank" title="It opens in new window">CrossRef
  5. Galazka, JM, Tian, C, Beeson, WT, Martinez, B, Glass, NL, Cate, JH (2010) Cellodextrin transport in yeast for improved biofuel production. Science 330: pp. 84-86 CrossRef
  6. Ha, SJ, Galazka, JM, Kim, SR, Choi, JH, Yang, X, Seo, JH, Glass, NL, Cate, JH, Jin, YS (2011) Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose fermentation. Proc Natl Acad Sci U S A 108: pp. 504-509 456108" target="_blank" title="It opens in new window">CrossRef
  7. Ha, SJ, Wei, Q, Kim, SR, Galazka, JM, Cate, JH, Jin, YS (2011) Cofermentation of cellobiose and galactose by an engineered Saccharomyces cerevisiae strain. Appl Environ Microbiol 77: pp. 5822-5825 CrossRef
  8. Garcia Sanchez, R, Hahn-H盲gerdal, B, Gorwa-Grauslund, MF (2010) Cross-reactions between engineered xylose and galactose pathways in recombinant Saccharomyces cerevisiae. Biotechnol Biofuels 3: pp. 19 4-6834-3-19" target="_blank" title="It opens in new window">CrossRef
  9. Wisselink, HW, Toirkens, MJ, Wu, Q, Pronk, JT, Maris, AJ (2009) Novel evolutionary engineering approach for accelerated utilization of glucose, xylose, and arabinose mixtures by engineered Saccharomyces cerevisiae strains. Appl Environ Microbiol 75: pp. 907-914 CrossRef
  10. Hahn-H盲gerdal, B, Karhumaa, K, Fonseca, C, Spencer-Martins, I, Gorwa-Grauslund, MF (2007) Towards industrial pentose-fermenting yeast strains. Appl Microbiol Biotechnol 74: pp. 937-953 CrossRef
  11. Du, J, Yuan, Y, Si, T, Lian, J, Zhao, H (2012) Customized optimization of metabolic pathways by combinatorial transcriptional engineering. Nucleic Acids Res 40: pp. e142 49" target="_blank" title="It opens in new window">CrossRef
  12. Bae, YH, Kang, KH, Jin, YS, Seo, JH (2014) Molecular cloning and expression of fungal cellobiose transporters and beta-glucosidases conferring efficient cellobiose fermentation in Saccharomyces cerevisiae. J Biotechnol 169: pp. 34-41 CrossRef
  13. Ha, SJ, Kim, SR, Kim, H, Du, J, Cate, JH, Jin, YS (2013) Continuous co-fermentation of cellobiose and xylose by engineered Saccharomyces cerevisiae. Bioresour Technol 149: pp. 525-531 CrossRef
  14. Eriksen, DT, Hsieh, PC, Lynn, P, Zhao, H (2013) Directed evolution of a cellobiose utilization pathway in Saccharomyces cerevisiae by simultaneously engineering multiple proteins. Microb Cell Factories 12: pp. 61 475-2859-12-61" target="_blank" title="It opens in new window">CrossRef
  15. Zaman, S, Lippman, SI, Zhao, X, Broach, JR (2008) How Saccharomyces responds to nutrients. Annu Rev Genet 42: pp. 27-81 46/annurev.genet.41.110306.130206" target="_blank" title="It opens in new window">CrossRef
  16. Busti, S, Coccetti, P, Alberghina, L, Vanoni, M (2010) Glucose signaling-mediated coordination of cell growth and cell cycle in Saccharomyces cerevisiae. Sensors (Basel) 10: pp. 6195-6240 CrossRef
  17. Gelad茅, R, Velde, S, Dijck, P, Thevelein, JM (2003) Multi-level response of the yeast genome to glucose. Genome Biol 4: pp. 233 4-11-233" target="_blank" title="It opens in new window">CrossRef
  18. Rolland, F, Winderickx, J, Thevelein, JM (2002) Glucose-sensing and -signalling mechanisms in yeast. FEMS Yeast Res 2: pp. 183-201 4.2002.tb00084.x" target="_blank" title="It opens in new window">CrossRef
  19. Macneil, LT, Walhout, AJ (2011) Gene regulatory networks and the role of robustness and stochasticity in the control of gene expression. Genome Res 21: pp. 645-657 CrossRef
  20. G枚rke, B, St眉lke, J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6: pp. 613-624 CrossRef
  21. Zaman, S, Lippman, SI, Schneper, L, Slonim, N, Broach, JR (2009) Glucose regulates transcription in yeast through a network of signaling pathways. Mol Syst Biol 5: pp. 245 CrossRef
  22. Ozcan, S, Johnston, M (1999) Function and regulation of yeast hexose transporters. Microbiol Mol Biol Rev 63: pp. 554-569
  23. Gancedo, JM (1998) Yeast carbon catabolite repression. Microbiol Mol Biol Rev 62: pp. 334-361
  24. Palomino, A, Herrero, P, Moreno, F (2006) Tpk3 and Snf1 protein kinases regulate Rgt1 association with Saccharomyces cerevisiae HXK2 promoter. Nucleic Acids Res 34: pp. 1427-1438 CrossRef
  25. Yu, H, Gerstein, M (2006) Genomic analysis of the hierarchical structure of regulatory networks. Proc Natl Acad Sci U S A 103: pp. 14724-14731 CrossRef
  26. Lelli, KM, Slattery, M, Mann, RS (2012) Disentangling the many layers of eukaryotic transcriptional regulation. Annu Rev Genet 46: pp. 43-68 46/annurev-genet-110711-155437" target="_blank" title="It opens in new window">CrossRef
  27. Albert, FW, Treusch, S, Shockley, AH, Bloom, JS, Kruglyak, L (2014) Genetics of single-cell protein abundance variation in large yeast populations. Nature 506: pp. 494-497 4" target="_blank" title="It opens in new window">CrossRef
  28. Kummel, A, Ewald, JC, Fendt, SM, Jol, SJ, Picotti, P, Aebersold, R, Sauer, U, Zamboni, N, Heinemann, M (2010) Differential glucose repression in common yeast strains in response to HXK2 deletion. FEMS Yeast Res 10: pp. 322-332 4.2010.00609.x" target="_blank" title="It opens in new window">CrossRef
  29. Ha, SJ, Galazka, JM, Joong Oh, E, Kordic, V, Kim, H, Jin, YS, Cate, JH (2013) Energetic benefits and rapid cellobiose fermentation by Saccharomyces cerevisiae expressing cellobiose phosphorylase and mutant cellodextrin transporters. Metab Eng 15: pp. 134-143 CrossRef
  30. Ha, SJ, Kim, H, Lin, Y, Jang, MU, Galazka, JM, Kim, TJ, Cate, JH, Jin, YS (2013) Single amino acid substitutions in HXT2.4 from Scheffersomyces stipitis lead to improved cellobiose fermentation by engineered Saccharomyces cerevisiae. Appl Environ Microbiol 79: pp. 1500-1507 CrossRef
  31. Lian, J, Li, Y, HamediRad, M, Zhao, H (2014) Directed evolution of a cellodextrin transporter for improved biofuel production under anaerobic conditions in Saccharomyces cerevisiae. Biotechnol Bioeng 111: pp. 1521-1531 4" target="_blank" title="It opens in new window">CrossRef
  32. Sadie, CJ, Rose, SH, Haan, R, Zyl, WH (2011) Co-expression of a cellobiose phosphorylase and lactose permease enables intracellular cellobiose utilisation by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 90: pp. 1373-1380 4-z" target="_blank" title="It opens in new window">CrossRef
  33. Aeling, KA, Salmon, KA, Laplaza, JM, Li, L, Headman, JR, Hutagalung, AH, Picataggio, S (2012) Co-fermentation of xylose and cellobiose by an engineered Saccharomyces cerevisiae. J Ind Microbiol Biotechnol 39: pp. 1597-1604 CrossRef
  34. Pitk盲nen, J (2005) Impact of Xylose and Mannose on Central Metabolism of Yeast Saccharomyces cerevisiae. PhD thesis, Helsinki University of Technology, Department of Chemical Technology, 釁
  35. Rodr铆guez, A, Cera, T, Herrero, P, Moreno, F (2001) The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2 genes of Saccharomyces cerevisiae. Biochem J 355: pp. 625-631
  36. Carrillo, E, Ben-Ari, G, Wildenhain, J, Tyers, M, Grammentz, D, Lee, TA (2012) Characterizing the roles of Met31 and Met32 in coordinating Met4-activated transcription in the absence of Met30. Mol Biol Cell 23: pp. 1928-1942 CrossRef
  37. Nishimura, H, Kawasaki, Y, Kaneko, Y, Nosaka, K, Iwashima, A (1992) Cloning and characteristics of a positive regulatory gene, THI2 (PHO6), of thiamin biosynthesis in Saccharomyces cerevisiae. FEBS Lett 297: pp. 155-158 4-5793(92)80349-L" target="_blank" title="It opens in new window">CrossRef
  38. Zampar, GG, K眉mmel, A, Ewald, J, Jol, S, Niebel, B, Picotti, P, Aebersold, R, Sauer, U, Zamboni, N, Heinemann, M (2013) Temporal system-level organization of the switch from glycolytic to gluconeogenic operation in yeast. Mol Syst Biol 9: pp. 651 CrossRef
  39. Li, L, Bagley, D, Ward, DM, Kaplan, J (2008) Yap5 is an iron-responsive transcriptional activator that regulates vacuolar iron storage in yeast. Mol Cell Biol 28: pp. 1326-1337 CrossRef
  40. Andr茅, B (1990) The UGA3 gene regulating the GABA catabolic pathway in Saccharomyces cerevisiae codes for a putative zinc-finger protein acting on RNA amount. Mol Gen Genet 220: pp. 269-276 493" target="_blank" title="It opens in new window">CrossRef
  41. Lorenz, MC, Heitman, J (1998) Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains. Genetics 150: pp. 1443-1457
  42. Kurihara, LJ, Stewart, BG, Gammie, AE, Rose, MD (1996) Kar4p, a karyogamy-specific component of the yeast pheromone response pathway. Mol Cell Biol 16: pp. 3990-4002
  43. Westholm, JO, Nordberg, N, Mur茅n, E, Ameur, A, Komorowski, J, Ronne, H (2008) Combinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3. BMC Genomics 9: pp. 601 471-2164-9-601" target="_blank" title="It opens in new window">CrossRef
  44. Vincent, O, Carlson, M (1998) Sip4, a Snf1 kinase-dependent transcriptional activator, binds to the carbon source-responsive element of gluconeogenic genes. Embo J 17: pp. 7002-7008 CrossRef
  45. Charron, MJ, Dubin, RA, Michels, CA (1986) Structural and functional analysis of the MAL1 locus of Saccharomyces cerevisiae. Mol Cell Biol 6: pp. 3891-3899
  46. Magasanik, B, Kaiser, CA (2002) Nitrogen regulation in Saccharomyces cerevisiae. Gene 290: pp. 1-18 CrossRef
  47. Hofman-Bang, J (1999) Nitrogen catabolite repression in Saccharomyces cerevisiae. Mol Biotechnol 12: pp. 35-73 CrossRef
  48. Bourot, S, Karst, F (1995) Isolation and characterization of the Saccharomyces cerevisiae SUT1 gene involved in sterol uptake. Gene 165: pp. 97-102 478-O" target="_blank" title="It opens in new window">CrossRef
  49. R茅gnacq, M, Alimardani, P, Moudni, B, Berg猫s, T (2001) SUT1p interaction with Cyc8p(Ssn6p) relieves hypoxic genes from Cyc8p-Tup1p repression in Saccharomyces cerevisiae. Mol Microbiol 40: pp. 1085-1096 46/j.1365-2958.2001.02450.x" target="_blank" title="It opens in new window">CrossRef
  50. Mai, B, Breeden, L (1997) Xbp1, a stress-induced transcriptional repressor of the Saccharomyces cerevisiae Swi4/Mbp1 family. Mol Cell Biol 17: pp. 6491-6501
  51. Deng, Y, He, T, Wu, Y, Vanka, P, Yang, G, Huang, Y, Yao, H, Brown, SJ (2005) Computationally analyzing the possible biological function of YJL103C鈥揳n ORF potentially involved in the regulation of energy process in yeast. Int J Mol Med 15: pp. 123-127
  52. Hlynialuk, C, Schierholtz, R, Vernooy, A, Merwe, G (2008) Nsf1/Ypl230w participates in transcriptional activation during non-fermentative growth and in response to salt stress in Saccharomyces cerevisiae. Microbiology 154: pp. 2482-2491 CrossRef
  53. Ratnakumar, S, Kacherovsky, N, Arms, E, Young, ET (2009) Snf1 controls the activity of adr1 through dephosphorylation of Ser230. Genetics 182: pp. 735-745 4/genetics.109.103432" target="_blank" title="It opens in new window">CrossRef
  54. Young, ET, Dombek, KM, Tachibana, C, Ideker, T (2003) Multiple pathways are co-regulated by the protein kinase Snf1 and the transcription factors Adr1 and Cat8. J Biol Chem 278: pp. 26146-26158 4/jbc.M301981200" target="_blank" title="It opens in new window">CrossRef
  55. Sch眉ller, HJ (2003) Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae. Curr Genet 43: pp. 139-160
  56. Rahner, A, Sch枚ler, A, Martens, E, Gollwitzer, B, Sch眉ller, HJ (1996) Dual influence of the yeast Cat1p (Snf1p) protein kinase on carbon source-dependent transcriptional activation of gluconeogenic genes by the regulatory gene CAT8. Nucleic Acids Res 24: pp. 2331-2337 4.12.2331" target="_blank" title="It opens in new window">CrossRef
  57. Forsburg, SL, Guarente, L (1989) Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Genes Dev 3: pp. 1166-1178 CrossRef
  58. Brons, JF, Jong, M, Valens, M, Grivell, LA, Bolotin-Fukuhara, M, Blom, J (2002) Dissection of the promoter of the HAP4 gene in S. cerevisiae unveils a complex regulatory framework of transcriptional regulation. Yeast 19: pp. 923-932 CrossRef
  59. Hosaka, K, Nikawa, J, Kodaki, T, Yamashita, S (1992) A dominant mutation that alters the regulation of INO1 expression in Saccharomyces cerevisiae. J Biochem 111: pp. 352-358
  60. Kim, SR, Skerker, JM, Kang, W, Lesmana, A, Wei, N, Arkin, AP, Jin, YS (2013) Rational and evolutionary engineering approaches uncover a small set of genetic changes efficient for rapid xylose fermentation in Saccharomyces cerevisiae. PLoS One 8: pp. e57048 48" target="_blank" title="It opens in new window">CrossRef
  61. Wei, N, Quarterman, J, Kim, SR, Cate, JH, Jin, YS (2013) Enhanced biofuel production through coupled acetic acid and xylose consumption by engineered yeast. Nat Commun 4: pp. 2580
  62. Fiaux, J, Cakar, ZP, Sonderegger, M, W眉thrich, K, Szyperski, T, Sauer, U (2003) Metabolic-flux profiling of the yeasts Saccharomyces cerevisiae and Pichia stipitis. Eukaryot Cell 2: pp. 170-180 CrossRef
  63. Blazeck, J, Alper, HS (2013) Promoter engineering: recent advances in controlling transcription at the most fundamental level. Biotechnol J 8: pp. 46-58 CrossRef
  64. Zhou, H, Cheng, JS, Wang, BL, Fink, GR, Stephanopoulos, G (2012) Xylose isomerase overexpression along with engineering of the pentose phosphate pathway and evolutionary engineering enable rapid xylose utilization and ethanol production by Saccharomyces cerevisiae. Metab Eng 14: pp. 611-622 CrossRef
  65. Scalcinati, G, Otero, JM, Vleet, JR, Jeffries, TW, Olsson, L, Nielsen, J (2012) Evolutionary engineering of Saccharomyces cerevisiae for efficient aerobic xylose consumption. FEMS Yeast Res 12: pp. 582-597 4.2012.00808.x" target="_blank" title="It opens in new window">CrossRef
  66. Versele, M, Winde, JH, Thevelein, JM (1999) A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose-activation of the cAMP pathway through direct inhibition of Gpa2. Embo J 18: pp. 5577-5591 CrossRef
  67. Ma, P, Wera, S, Dijck, P, Thevelein, JM (1999) The PDE1-encoded low-affinity phosphodiesterase in the yeast Saccharomyces cerevisiae has a specific function in controlling agonist-induced cAMP signaling. Mol Biol Cell 10: pp. 91-104 CrossRef
  68. Kaniak, A, Xue, Z, Macool, D, Kim, JH, Johnston, M (2004) Regulatory network connecting two glucose signal transduction pathways in Saccharomyces cerevisiae. Eukaryot Cell 3: pp. 221-231 4" target="_blank" title="It opens in new window">CrossRef
  69. Salusj盲rvi, L, Kankainen, M, Soliymani, R, Pitk盲nen, JP, Penttil盲, M, Ruohonen, L (2008) Regulation of xylose metabolism in recombinant Saccharomyces cerevisiae. Microb Cell Factories 7: pp. 18 475-2859-7-18" target="_blank" title="It opens in new window">CrossRef
  70. Jin, YS, Laplaza, JM, Jeffries, TW (2004) Saccharomyces cerevisiae engineered for xylose metabolism exhibits a respiratory response. Appl Environ Microbiol 70: pp. 6816-6825 4" target="_blank" title="It opens in new window">CrossRef
  71. Pel谩ez, R, Herrero, P, Moreno, F (2010) Functional domains of yeast hexokinase 2. Biochem J 432: pp. 181-190 42/BJ20100663" target="_blank" title="It opens in new window">CrossRef
  72. DelaFuente, G (1970) Specific inactivation of yeast hexokinase induced by xylose in the presence of a phosphoryl donor substrate. Eur J Biochem 16: pp. 240-243 432-1033.1970.tb01077.x" target="_blank" title="It opens in new window">CrossRef
  73. Fern谩ndez, R, Herrero, P, Moreno, F (1985) Inhibition and inactivation of glucose-phosphorylating enzymes from Saccharomyces cerevisiae by D-xylose. J Gen Microbiol 131: pp. 2705-2709
  74. Bergdahl, B, Sandstr枚m, AG, Borgstr枚m, C, Boonyawan, T, Niel, EW, Gorwa-Grauslund, MF (2013) Engineering yeast hexokinase 2 for improved tolerance toward xylose-induced inactivation. PLoS One 8: pp. e75055 CrossRef
  75. Ness, F, Bourot, S, R茅gnacq, M, Spagnoli, R, Berg猫s, T, Karst, F (2001) SUT1 is a putative Zn[II]2Cys6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae cells. Eur J Biochem 268: pp. 1585-1595 46/j.1432-1327.2001.02029.x" target="_blank" title="It opens in new window">CrossRef
  76. Alimardani, P, R茅gnacq, M, Moreau-Vauzelle, C, Ferreira, T, Rossignol, T, Blondin, B, Berg猫s, T (2004) SUT1-promoted sterol uptake involves the ABC transporter Aus1 and the mannoprotein Dan1 whose synergistic action is sufficient for this process. Biochem J 381: pp. 195-202 42/BJ20040297" target="_blank" title="It opens in new window">CrossRef
  77. Foster, HA, Cui, M, Naveenathayalan, A, Unden, H, Schwanbeck, R, H枚fken, T (2013) The zinc cluster protein Sut1 contributes to filamentation in Saccharomyces cerevisiae. Eukaryot Cell 12: pp. 244-253 4-12" target="_blank" title="It opens in new window">CrossRef
  78. Maris, AJ, Bakker, BM, Brandt, M, Boorsma, A, Mattos, MJT, Grivell, LA, Pronk, JT, Blom, J (2001) Modulating the distribution of fluxes among respiration and fermentation by overexpression of HAP4 in Saccharomyces cerevisiae. FEMS Yeast Res 1: pp. 139-149 4.2001.tb00025.x" target="_blank" title="It opens in new window">CrossRef
  79. Soontorngun, N, Baramee, S, Tangsombatvichit, C, Thepnok, P, Cheevadhanarak, S, Robert, F, Turcotte, B (2012) Genome-wide location analysis reveals an important overlap between the targets of the yeast transcriptional regulators Rds2 and Adr1. Biochem Biophys Res Commun 423: pp. 632-637 CrossRef
  80. Bertram, PG, Choi, JH, Carvalho, J, Chan, TF, Ai, W, Zheng, XF (2002) Convergence of TOR-nitrogen and Snf1-glucose signaling pathways onto Gln3. Mol Cell Biol 22: pp. 1246-1252 4.1246-1252.2002" target="_blank" title="It opens in new window">CrossRef
  81. Mittal, N, Roy, N, Babu, MM, Janga, SC (2009) Dissecting the expression dynamics of RNA-binding proteins in posttranscriptional regulatory networks. Proc Natl Acad Sci U S A 106: pp. 20300-20305 40106" target="_blank" title="It opens in new window">CrossRef
  82. Gerashchenko, MV, Lobanov, AV, Gladyshev, VN (2012) Genome-wide ribosome profiling reveals complex translational regulation in response to oxidative stress. Proc Natl Acad Sci U S A 109: pp. 17394-17399 CrossRef
  83. Bergdahl, B, Heer, D, Sauer, U, Hahn-H盲gerdal, B, Niel, EW (2012) Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose. Biotechnol Biofuels 5: pp. 34 4-6834-5-34" target="_blank" title="It opens in new window">CrossRef
  84. Unger, T, Jacobovitch, Y, Dantes, A, Bernheim, R, Peleg, Y (2010) Applications of the restriction free (RF) cloning procedure for molecular manipulations and protein expression. J Struct Biol 172: pp. 34-44 CrossRef
  85. Tian, C, Beeson, WT, Iavarone, AT, Sun, J, Marletta, MA, Cate, JH, Glass, NL (2009) Systems analysis of plant cell wall degradation by the model filamentous fungus Neurospora crassa. Proc Natl Acad Sci U S A 106: pp. 22157-22162 CrossRef
  86. Christianson, TW, Sikorski, RS, Dante, M, Shero, JH, Hieter, P (1992) Multifunctional yeast high-copy-number shuttle vectors. Gene 110: pp. 119-122 454-W" target="_blank" title="It opens in new window">CrossRef
  87. Sikorski, RS, Hieter, P (1989) A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122: pp. 19-27
  88. G眉ldener, U, Heck, S, Fielder, T, Beinhauer, J, Hegemann, JH (1996) A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 24: pp. 2519-2524 4.13.2519" target="_blank" title="It opens in new window">CrossRef
  89. Darby, RA, Cartwright, SP, Dilworth, MV, Bill, RM (2012) Which yeast species shall I choose? Saccharomyces cerevisiae versus Pichia pastoris (review). Methods Mol Biol 866: pp. 11-23 CrossRef
  90. Hanscho, M, Ruckerbauer, DE, Chauhan, N, Hofbauer, HF, Krahulec, S, Nidetzky, B, Kohlwein, SD, Zanghellini, J, Natter, K (2012) Nutritional requirements of the BY series of Saccharomyces cerevisiae strains for optimum growth. FEMS Yeast Res 12: pp. 796-808 4.2012.00830.x" target="_blank" title="It opens in new window">CrossRef
  91. RefSeq: NCBI Reference Sequence Database. [http://www.ncbi.nlm.nih.gov/refseq/]
  92. Bolstad, BM, Irizarry, RA, Astrand, M, Speed, TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: pp. 185-193 CrossRef
  93. Gene Expression Omnibus. [http://www.ncbi.nlm.nih.gov/geo/]
  94. Gene Ontology Consortium: Download Annotations. [http://www.geneontology.org/GO.current.annotations.shtml]
  95. Baggerly, KA, Deng, L, Morris, JS, Aldaz, CM (2003) Differential expression in SAGE: accounting for normal between-library variation. Bioinformatics 19: pp. 1477-1483 CrossRef
  96. Johnson, VE (2013) Revised standards for statistical evidence. Proc Natl Acad Sci U S A 110: pp. 19313-19317 476110" target="_blank" title="It opens in new window">CrossRef
  97. FunSpec: a web-based cluster interpreter for yeast. [http://funspec.med.utoronto.ca/]
  98. Robinson, MD, Grigull, J, Mohammad, N, Hughes, TR (2002) FunSpec: a web-based cluster interpreter for yeast. BMC Bioinformatics 3: pp. 35 471-2105-3-35" target="_blank" title="It opens in new window">CrossRef
  99. David, F, Berger, A, H盲nsch, R, Rohde, M, Franco-Lara, E (2011) Single cell analysis applied to antibody fragment production with Bacillus megaterium: development of advanced physiology and bioprocess state estimation tools. Microb Cell Factories 10: pp. 23 475-2859-10-23" target="_blank" title="It opens in new window">CrossRef
  100. Wisselink, HW, Toirkens, MJ, Rosario Franco Berriel, M, Winkler, AA, Dijken, JP, Pronk, JT, Maris, AJ (2007) Engineering of Saccharomyces cerevisiae for efficient anaerobic alcoholic fermentation of L-arabinose. Appl Environ Microbiol 73: pp. 4881-4891 CrossRef
  101. Motulsky, HJ, Christopoulos, A (2003) Fitting models to biological data using linear and nonlinear regression. A practical guide to curve fitting. GraphPad Software Inc., San Diego, CA
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Biotechnology
  Plant Breeding/Biotechnology
  Renewable and Green Energy
  Environmental Engineering/Biotechnology
  
• 出版者：BioMed Central
• ISSN：1754-6834

文摘

Background Saccharomyces cerevisiae, a key organism used for the manufacture of renewable fuels and chemicals, has been engineered to utilize non-native sugars derived from plant cell walls, such as cellobiose and xylose. However, the rates and efficiencies of these non-native sugar fermentations pale in comparison with those of glucose. Systems biology methods, used to understand biological networks, hold promise for rational microbial strain development in metabolic engineering. Here, we present a systematic strategy for optimizing non-native sugar fermentation by recombinant S. cerevisiae, using cellobiose as a model. Results Differences in gene expression between cellobiose and glucose metabolism revealed by RNA deep sequencing indicated that cellobiose metabolism induces mitochondrial activation and reduces amino acid biosynthesis under fermentation conditions. Furthermore, glucose-sensing and signaling pathways and their target genes, including the cAMP-dependent protein kinase A pathway controlling the majority of glucose-induced changes, the Snf3-Rgt2-Rgt1 pathway regulating hexose transport, and the Snf1-Mig1 glucose repression pathway, were at most only partially activated under cellobiose conditions. To separate correlations from causative effects, the expression levels of 19 transcription factors perturbed under cellobiose conditions were modulated, and the three strongest promoters under cellobiose conditions were applied to fine-tune expression of the heterologous cellobiose-utilizing pathway. Of the changes in these 19 transcription factors, only overexpression of SUT1 or deletion of HAP4 consistently improved cellobiose fermentation. SUT1 overexpression and HAP4 deletion were not synergistic, suggesting that SUT1 and HAP4 may regulate overlapping genes important for improved cellobiose fermentation. Transcription factor modulation coupled with rational tuning of the cellobiose consumption pathway significantly improved cellobiose fermentation. Conclusions We used systems-level input to reveal the regulatory mechanisms underlying suboptimal metabolism of the non-glucose sugar cellobiose. By identifying key transcription factors that cause suboptimal cellobiose fermentation in engineered S. cerevisiae, and by fine-tuning the expression of a heterologous cellobiose consumption pathway, we were able to greatly improve cellobiose fermentation by engineered S. cerevisiae. Our results demonstrate a powerful strategy for applying systems biology methods to rapidly identify metabolic engineering targets and overcome bottlenecks in performance of engineered strains.