Metabolic engineering of Saccharomyces cerevisiae for production of carboxylic acids: Current status and challenges

FEMS Yeast Research

Volumn 9, Issue 8, 2009, Pages 1123-1136

  Abbott, Derek A ^a,b   Zelle, Rintze M ^a,b   Pronk, Jack T ^a,b   Van Maris, Antonius J A ^a,b  

^a DELFT UNIVERSITY OF TECHNOLOGY   (Netherlands)

^b KLUYVER CENTRE FOR GENOMICS OF INDUSTRIAL FERMENTATION   (Netherlands)

Author keywords

Lactate; Malate; Pyruvate; Succinate; Tolerance; Transport

Indexed keywords

ALCOHOL; CARBON; CARBON DIOXIDE; CARBOXYLIC ACID DERIVATIVE; GLUCOSE; LACTIC ACID; MALIC ACID; PYRUVIC ACID; SUCCINIC ACID;

BIOCATALYST; CARBON DIOXIDE FIXATION; DNA MODIFICATION; ENERGY TRANSFER; FERMENTATION; FUNGAL STRAIN; GENE DELETION; GENETIC ENGINEERING; METABOLIC ENGINEERING; NONHUMAN; PH; PROTEIN EXPRESSION; SACCHAROMYCES CEREVISIAE; SCHIZOSACCHAROMYCES POMBE; SHORT SURVEY;

CARBOXYLIC ACIDS; GENETIC ENGINEERING; INDUSTRIAL MICROBIOLOGY; METABOLIC NETWORKS AND PATHWAYS; SACCHAROMYCES CEREVISIAE;

SACCHAROMYCES CEREVISIAE;

EID: 70350521215     PISSN: 15671356     EISSN: 15671364     Source Type: Journal    
DOI: 10.1111/j.1567-1364.2009.00537.x     Document Type: Short Survey

References (128)

1. Abbott DA, Knijnenburg TA, de Poorter LMI, Reinders MJT, Pronk JT van Maris AJA (2007) Generic and specific transcriptional responses to different weak organic acids in anaerobic chemostat cultures of Saccharomyces cerevisiae. FEMS Yeast Res 7 : 819 833.
2. Abbott DA, Suir E, van Maris AJA Pronk JT (2008) Physiological and transcriptional responses to high concentrations of lactic acid in anaerobic chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microb 74 : 5759 5768.
3. Abbott DA, van den Brink J, Minneboo IMK, Pronk JT van Maris AJA (2009) Anaerobic homolactate fermentation with Saccharomyces cerevisiae results in depletion of ATP and impaired metabolic activity. FEMS Yeast Res 9 : 349 357.
4. Abe S, Furuya A, Saito T Takayama K (1962) Method of producing l-malic acid by fermentation. US Patent 3063910.
5. Adachi E, Torigoe M, Sugiyama M, Nikawa JI Shimizu K (1998) Modification of metabolic pathways of Saccharomyces cerevisiae by the expression of lactate dehydrogenase and deletion of pyruvate decarboxylase genes for the lactic acid fermentation at low pH value. J Ferment Bioeng 86 : 284 289.
6. Ali MA Konishi T (1998) Enhancement of hydroxyl radical generation in the Fenton reaction by alpha-hydroxy acid. Biochem Mol Biol Int 46 : 137 145.
7. Ali MA, Yasui F, Matsugo S Konishi T (2000) The lactate-dependent enhancement of hydroxyl radical generation by the Fenton reaction. Free Radical Res 32 : 429 438.
8. Almeida JRM, Modig T, Petersson A, Hähn-Hägerdal B, Lidén G Gorwa-Grauslund MF (2007) Increased tolerance and conversion on inhibitors in lignocellulosic hydrolysates by Saccharomyces cerevisiae. J Chem Technol Biot 82 : 340 349.
9. Alper H Stephanopoulos G (2007) Global transcription machinery engineering: a new approach for improving cellular phenotype. Metab Eng 9 : 258 267.
10. Alper H, Moxley J, Nevoigt E, Fink GR Stephanopoulos G (2006) Engineering yeast transcription machinery for improved ethanol tolerance and production. Science 314 : 1565 1568.
11. Ansanay V, Dequin S, Camarasa C, Schaeffer V, Grivet JP, Blondin B, Salmon J-M Barre P (1998) Malolactic fermentation by engineered Saccharomyces cerevisiae as compared with engineered Schizosaccharomyces pombe. Yeast 12 : 215 225.
12. Arikawa Y, Kobayashi M, Kodaira R, Shimosaka M, Muratsubaki H, Enomoto K Okazaki M (1999) Isolation of sake yeast strains possessing various levels of succinate- and/or malate-producing abilities by gene disruption or mutation. J Biosci Bioeng 87 : 333 339.
13. Bailey JE (1991) Toward a science of metabolic engineering. Science 252 : 1668 1675.
14. Battat E, Peleg Y, Bercovitz A, Rokem JS Goldberg I (1991) Optimization of l-malic acid production by Aspergillus flavus in a stirred fermenter. Biotechnol Bioeng 37 : 1108 1116.
15. Benninga H A (1990) The History of Lactic Acid Making. Kluwer Academic Publishers, Dordrecht, the Netherlands.
16. Blomqvist K, Suihko ML, Knowles J Penttilä M (1991) Chromosomal integration and expression of two bacterial α-acetolactate decarboxylase genes in brewer's yeast. Appl Environ Microb 57 : 2796 2803.
17. Boles E, Bill R, Gustafsson L, Hohmann S, Larsson C Otterstedt K (2001) Recombinant Saccharomyces cerevisiae expressing chimeric glucose transporters. Patent WO02/00880.
18. Branduardi P, Sauer M, De Gioia L, Zampella G, Valli M, Mattanovich D Porro D (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 15.
19. Branduardi P, Fossati T, Sauer M, Pagani R, Mattanovich D Porro D (2007) Biosynthesis of vitamin C by yeast leads to increased stress resistance. PLoS One 2 : e1092.
20. Branduardi P, Smeraldi C Porro D (2008) Metabolically engineered yeasts: 'potential' industrial applications. J Mol Microb Biotech 15 : 31 40.
21. BREW (2006) Medium and long-term opportunities and risks of the biotechnological production of bulk chemicals from renewable resources - final report. Prepared under the European Commissions GROWTH program, Utrecht, September 2006.
22. Brewster NK, Val DL, Walker ME Wallace JC (1994) Regulation of pyruvate carboxylase isozyme (PYC1, PYC2) gene expression in Saccharomyces cerevisiae during fermentative and nonfermentative growth. Arch Biochem Biophys 311 : 62 71.
23. Camarasa C, Bidard F, Bony M, Barre P Dequin S (2001) Characterization of Schizosaccharomyces pombe malate permease by expression in Saccharomyces cerevisiae. Appl Environ Microb 67 : 4144 4151.
24. Canonaco F, Schlattner U, Pruett PS, Wallimann T Sauer U (2002) Functional expression of phosphagen kinase systems confers resistance to transient stresses in Saccharomyces cerevisiae by buffering the ATP pool. J Biol Chem 277 : 31303 31309.
25. Casal M, Paiva S, Queirós O Soares-Silva I (2008) Transport of carboxylic acids in yeasts. FEMS Microbiol Rev 32 : 974 994.
26. Chopin A (1993) Organization and regulation of genes for amino acid biosynthesis in lactic acid bacteria. FEMS Microbiol Rev 12 : 21 38. (Pubitemid 223004839)
27. Chu BCH Lee H (2007) Genetic improvement of Saccharomyces cerevisiae for xylose fermentation. Biotechnol Adv 25 : 425 441.
28. Datta R, Tsai SP, Bonsignore P, Moon SH Frank JR (1995) Technological and economic potential of poly(lactic acid) and lactic acid derivatives. FEMS Microbiol Rev 16 : 221 231.
29. Davies CR, Wibowo W, Eschenbruch R, Lee TH Fleet GH (1985) Practical implications of malolactic fermentation: a review. Am J Enol Viticult 36 : 290 301.
30. de Jong-Gubbels P, Bauer J, Niederberger P, Stückrath I, Kötter P, van Dijken JP Pronk JT (1998) Physiological characterisation of a pyruvate-carboxylase-negative Saccharomyces cerevisiae mutant in batch and chemostat cultures. Antonie van Leeuwenhoek 74 : 253 263.
31. Dequin S Barre P (1994) Mixed lactic acid-alcoholic fermentation by Saccharomyces cerevisiae expressing the Lactobacillus casei l(+)-LDH. Biotechnology 12 : 173 177.
32. Diderich JA, Raamsdonk LM, Kruckeberg AL, Berden JA van Dam K (2001) Physiological properties of Saccharomyces cerevisiae from which hexokinase II has been deleted. Appl Environ Microb 67 : 1587 1593.
33. Do AH Choi DK (2007) Aflatoxins: detection, toxicity and biosynthesis. Biotechnol Bioproc E 12 : 585 593.
34. Donalies UEB, Nguyen HTT, Stahl U Nevoigt E (2008) Improvement of Saccharomyces yeast strains used in brewing, wine making and baking. Adv Biochem Eng Biot 111 : 67 98.
35. Drewke C, Thielen J Ciriacy M (1990) Ethanol formation in adh0 mutants reveals the existence of a novel acetaldehyde-reducing activity in Saccharomyces cerevisiae. J Bacteriol 172 : 3909 3917.
36. Eraso P Gancedo C (1987) Activation of yeast plasma membrane ATPase by acid pH during growth. FEBS Lett 224 : 187 192.
37. Fatichenti F, Farris GA, Deiana P Ceccarelli S (1984) Malic acid production and consumption by selected of Saccharomyces cerevisiae under anaerobic and aerobic conditions. Appl Microbiol Biot 19 : 427 429.
38. Fernandes AR, Mira NP, Vargas RC, Canelhas I Sá-Correia I (2005) Saccharomyces cerevisiae adaptation to weak acids involves the transcription factor Haa1p and Haa1p-regulated genes. Biochem Bioph Res Co 337 : 95 103.
39. Flikweert MT, van der Zanden L, Janssen WMTM, Steensma HY, Van Dijken JP Pronk JT (1996) Pyruvate decarboxylase: an indispensable enzyme for growth of Saccharomyces cerevisiae on glucose. Yeast 12 : 247 257.
40. Flikweert MT, van Dijken JP Pronk JT (1997) Metabolic responses of pyruvate decarboxylase-negative Saccharomyces cerevisiae to glucose excess. Appl Environ Microb 63 : 3399 3404.
41. Flikweert MT, de Swaaf M, van Dijken JP Pronk JT (1999) Growth requirements of pyruvate-decarboxylase-negative Saccharomyces cerevisiae. FEMS Microbiol Lett 174 : 73 79.
42. Gárdonyi M Hahn-Hägerdal B (2003) The Streptomyces rubiginosus xylose isomerase is misfolded when expressed in Saccharomyces cerevisiae. Enzyme Microb Tech 32 : 252 259.
43. Giannattasio S, Guaragnella N, Corte-Real M, Passarella S Marra E (2005) Acid stress adaptation protects Saccharomyces cerevisiae from acetic acid-induced programmed cell death. Gene 354 : 93 98.
44. 1 redox couple regulates mitochondrial oxygen radical formation. Arch Biochem Biophys 388 : 34 38.
45. Gregori C, Bauer B, Schwartz C, Kren A, Schüller C Kuchler K (2007) A genetic screen identifies mutations in the yeast WAR1 gene, linking transcription factor phosphorylation to weak-acid stress adaptation. Eur J Biochem 274 : 3094 3107.
46. Guijarro JM Lagunas R (1984) Saccharomyces cerevisiae does not accumulate ethanol against a concentration gradient. J Bacteriol 160 : 874 878.
47. Hähn-Hägerdal B, Karhumaa K, Fonseca C, Spencer-Martins I Gorwa-Grauslund M (2007) Towards industrial pentose-fermenting yeast strains. Appl Microbiol Biot 74 : 937 953.
48. Hazan R, Levine A Abeliovich H (2004) Benzoic acid, a weak organic acid food preservative, exerts specific effects on intracellular membrane trafficking pathways in Saccharomyces cerevisiae. Appl Environ Microb 70 : 4449 4457.
49. Hesseltine CW, Shotwell OL, Ellis JJ Stubblefield RD (1966) Aflatoxin formation by Aspergillus flavus. Microbiol Mol Biol R 30 : 795 805.
50. Hohmann S (1991) Characterization of PDC6, a third structural gene for pyruvate decarboxylase in Saccharomyces cerevisiae. J Bacteriol 173 : 7963 7969.
51. +-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak-acid preservative sorbic acid. Appl Environ Microb 62 : 3158 3164.
52. Holyoak CD, Bracey D, Piper PW, Kuchler K Coote PJ (1999) The Saccharomyces cerevisiae weak-acid-inducible ABC transporter Pdr12 transports fluorescein and preservative anions from the cytosol by an energy-dependent mechanism. J Bacteriol 181 : 4644 4652.
53. Husnik JI, Volschenk H, Bauer J, Colavizza D, Luo Z van Vuuren HJJ (2006) Metabolic engineering of malolactic wine yeast. Metab Eng 8 : 315 323.
54. Ishida N, Saitoh S, Ohnishi T, Tokuhiro K, Nagamori E, Kitamoto K Takahashi H (2006a) Metabolic engineering of Saccharomyces cerevisiae for efficient production of pure l -(+)-lactic acid. Appl Biochem Biotech 129-132 : 795 807.
55. Ishida N, Suzuki T, Tokuhiro K, Nagamori E, Onishi T, Saitoh S, Kitamoto K Takahashi H (2006b) d-Lactic acid production by metabolically engineered Saccharomyces cerevisiae. J Biosci Bioeng 101 : 172 177.
56. Jantama K, Haupt MJ, Svoronos SA, Zhang XL, Moore JC, Shanmugam KT Ingram LO (2008a) Combining metabolic engineering and metabolic evolution to develop nonrecombinant strains of Escherichia coli C that produce succinate and malate. Biotechnol Bioeng 99 : 1140 1153.
57. Jantama K, Zhang XL, Moore JC, Shanmugam KT, Svoronos SA Ingram LO (2008b) Eliminating side products and increasing succinate yields in engineered strains of Escherichia coli C. Biotechnol Bioeng 101 : 881 893.
58. Klein CJL, Rasmussen JJ, Rønnow B, Olsson L Nielsen J (1999) Investigation of the impact of MIG1 and MIG2 on the physiology of Saccharomyces cerevisiae. J Biotechnol 68 : 197 212.
59. Klein-Marcuschamer D Stephanopoulos G (2008) Assessing the potential of mutational strategies to elicit new phenotypes in industrial strains. P Natl Acad Sci USA 105 : 2319 2324.
60. Krebs HA, Wiggins D, Stubbs M, Sols A Bedoya F (1983) Studies on the mechanism of the antifungal action of benzoate. Biochem J 214 : 657 663.
61. Kren A, Mamnun YM, Bauer BE, Schüller C, Wolfger H, Hatzixanthis K, Mollapour M, Gregori C, Piper P Kuchler K (2003) War1p, a novel transcription factor controlling weak acid stress response in yeast. Mol Cell Biol 23 : 1775 1785.
62. Liu C L Lievense J C (2005) Lactic acid producing yeast. Patent WO2005052174.
63. Ludovico P, Sousa MJ, Silva MT, Leão C Côrte-Real M (2001) Saccharomyces cerevisiae commits to a programmed cell death process in response to acetic acid. Microbiology 147 : 2409 2415. (Pubitemid 32899237)
64. Martins AM, Cordeiro CA Ponces Freire AM (2001) In situ analysis of methylglyoxal metabolism in Saccharomyces cerevisiae. FEBS Lett 499 : 41 44.
65. McAlister-Henn L, Steffan JS, Minard KI Anderson SL (1995) Expression and function of a mislocalized form of peroxisomal malate dehydrogenase (MDH3) in yeast. J Biol Chem 270 : 21220 21225.
66. McKinlay J, Vieille C Zeikus J (2007) Prospects for a bio-based succinate industry. Appl Microbiol Biot 76 : 727 740.
67. Minard KI McAlister-Henn L (1992) Glucose-induced degradation of the MDH2 isozyme of malate dehydrogenase in yeast. J Biol Chem 267 : 17458 17464.
68. Mollapour M Piper PW (2007) Hog1 MAP kinase phosphorylation targets the yeast Fps1 aquaglyceroporin for endocytosis, thereby rendering cells resistant to acetic acid. Mol Cell Biol 27 : 6446 6456.
69. Mollapour M, Fong D, Balakrishnan K, Harris N, Thompson S, Schüller C, Kuchler K Piper P (2004) Screening the yeast deletant mutant collection for hypersensitivity and hyper-resistance to sorbate, a weak organic acid food preservative. Yeast 21 : 927 946.
70. Mollapour M, Shepherd A Piper PW (2008) Novel stress responses facilitate Saccharomyces cerevisiae growth in the presence of the monocarboxylate preservatives. Yeast 25 : 169 177.
71. Nevoigt E (2008) Progress in metabolic engineering of Saccharomyces cerevisiae. Microbiol Mol Biol R 72 : 379 412.
72. Ostergaard S, Olsson L Nielsen J (2000) Metabolic engineering of Saccharomyces cerevisiae. Microbiol Mol Biol R 64 : 34 50.
73. Özcan S Johnston M (1999) Function and regulation of yeast hexose transporters. Microbiol Mol Biol R 63 : 554 569.
74. Pampulha ME Loureiro-Dias MC (1989) Combined effect of acetic acid, pH and ethanol on intracellular pH of fermenting yeast. Appl Microbiol Biot 31 : 547 550.
75. Pampulha ME Loureiro-Dias MC (1990) Activity of glycolytic enzymes of Saccharomyces cerevisiae in the presence of acetic acid. Appl Microbiol Biot 34 : 375 380.
76. Papagianni M (2007) Advances in citric acid fermentation by Aspergillus niger: biochemical aspects, membrane transport and modeling. Biotechnol Adv 25 : 244 263.
77. Patil K, Rocha I, Förster J Nielsen J (2005) Evolutionary programming as a platform for in silico metabolic engineering. BMC Bioinformatics 6 : 308 319.
78. Peleg Y, Stieglitz B Goldberg I (1988) Malic acid accumulation by Aspergillus flavus. Appl Microbiol Biot 28 : 69 75.
79. Pines O, Even-Ram S, Elnathan N, Battat E, Aharonov O, Gibson D Goldberg I (1996) The cytosolic pathway of l-malic acid synthesis in Saccharomyces cerevisiae: the role of fumarase. Appl Microbiol Biot 46 : 393 399.
80. Pines O, Shemesh S, Battat E Goldberg I (1997) Overexpression of cytosolic malate dehydrogenase (MDH2) causes overproduction of specific organic acids in Saccharomyces cerevisiae. Appl Microbiol Biot 48 : 248 255.
81. Piper P (1999) Yeast superoxide dismutase mutants reveal a pro-oxidant action of weak organic acid food preservatives. Free Radical Bio Med 27 : 1219 1227.
82. Piper P, Mahé Y, Thompson S, Pandjaitan R, Holyoak C, Egner R, Mühlbauer M, Coote P Kuchler K (1998) The Pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast. EMBO J 17 : 4257 4265.
83. Piper P, Calderon CO, Hatzixanthis K Mollapour M (2001) Weak acid adaptation: the stress response that confers yeasts with resistance to organic acid food preservatives. Microbiology 147 : 2635 2642. (Pubitemid 32976304)
84. Porro D, Brambilla L, Ranzi BM, Martegani E Alberghina L (1995) Development of metabolically engineered Saccharomyces cerevisiae cells for the production of lactic acid. Biotechnol Progr 11 : 294 298.
85. Porro D, Bianchi MM, Brambilla L et al 1999) Replacement of a metabolic pathway for large-scale production of lactic acid from engineered yeasts. Appl Environ Microb 65 : 4211 4215.
86. Porro D, Sauer M, Branduardi P Mattanovich D (2005) Recombinant protein production in yeasts. Mol Biotechnol 31 : 245 259.
87. Postma E, Verduyn C, Scheffers WA Van Dijken JP (1989) Enzymic analysis of the crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microb 55 : 468 477.
88. Pronk JT, Steensma HY van Dijken JP (1996) Pyruvate metabolism in Saccharomyces cerevisiae. Yeast 12 : 1607 1633.
89. Rapoport TA (2007) Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450 : 663 669.
90. Ro DK, Paradise EM, Ouellet M et al 2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440 : 940 943.
91. Russell AD (1991) Mechanisms of bacterial resistance to non-antibiotics: food additives and food and pharmaceutical preservatives. J Appl Bacteriol 71 : 191 201.
92. Sá-Correia I Tenreiro S (2002) The multidrug resistance transporters of the major facilitator superfamily, 6 years after disclosure of Saccharomyces cerevisiae genome sequence. J Biotechnol 98 : 215 226. (Pubitemid 34874547)
93. Saitoh S, Ishida N, Onishi T, Tokuhiro K, Nagamori E, Kitamoto K Takahashi H (2005) Genetically engineered wine yeast produces a high concentration of l-lactic acid of extremely high optical purity. Appl Environ Microb 71 : 2789 2792.
94. Salmond CV, Kroll RG Booth IR (1984) The effects of food preservatives on pH homeostasis in Escherichia coli. J Gen Microbiol 130 : 2845 2850.
95. Sauer M, Porro D, Mattanovich D Branduardi P (2008) Microbial production of organic acids: expanding the markets. Trends Biotechnol 26 : 100 108.
96. Sauer U (2001) Evolutionary engineering of industrially important microbial phenotypes. Advances in Biochemical Engineering/Biotechnology (Scheper Th., ed), pp. 129 169. Springer-Verlag, Heidelberg.
97. Sauer U Eikmanns BJ (2006) The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux distribution in bacteria. FEMS Microbiol Rev 29 : 765 794.
98. Schüller C, Mamnun YM, Mollapour M, Krapf G, Schuster M, Bauer BE, Piper PW Kuchler K (2004) Global phenotypic analysis and transcriptional profiling defines the weak acid stress response regulon in Saccharomyces cerevisiae. Mol Biol Cell 15 : 706 720.
99. Schwartz H Radler F (1988) Formation of l (-) malate by Saccharomyces cerevisiae during fermentation. Appl Microbiol Biot 27 : 553 560.
100. Singh SK, Ahmed SU Pandey A (2006) Metabolic engineering approaches for lactic acid production. Process Biochem 41 : 991 1000.
101. Skory C (2003) Lactic acid production by Saccharomyces cerevisiae expressing a Rhizopus oryzae lactate dehydrogenase gene. J Ind Microbiol Biot 30 : 22 27.
102. Song H Lee SY (2006) Production of succinic acid by bacterial fermentation. Enzyme Microb Tech 39 : 352 361.
103. Stucka R, Dequin S, Salmon JM Gancedo C (1991) DNA sequences in chromosomes 11 and VII code for pyruvate carboxylase isoenzymes in Saccharomyces cerevisiae: analysis of pyruvate carboxylase-deficient strains. Mol Gen Genet 229 : 307 315.
104. 1 complex. Arch Biochem Biophys 419 : 198 206.
105. Szczebara FM, Chandelier C, Villeret C et al 2003) Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Nat Biotechnol 21 : 143 149.
106. Tanghe A, Van Dijck P, Dumortier F, Teunissen A, Hohmann S Thevelein JM (2002) Aquaporin expression correlates with freeze tolerance in baker's yeast, and overexpression improves freeze tolerance in industrial strains. Appl Environ Microb 68 : 5981 5989.
107. Tarrío N, García-Leiro A, Cerdan ME González-Siso MI (2008) The role of glutathione reductase in the interplay between oxidative stress response and turnover of cytosolic NADPH in Kluyveromyces lactis. FEMS Yeast Res 8 : 597 606.
108. Vaidya AN, Pandey RA, Mudliar S, Suresh Kumar M, Chakrabarti T Devotta S (2005) Production and recovery of lactic acid for polylactide - an overview. Crit Rev Env Sci Tec 35 : 429 467.
109. van den Berg MA, de Jong-Gubbels P Steensma HY (1998) Transient mRNA responses in chemostat cultures as a method of defining putative regulatory elements: application to genes involved in Saccharomyces cerevisiae acetyl-coenzyme A metabolism. Yeast 14 : 1089 1104.
110. van Dijken JP Scheffers WA (1986) Redox balances in the metabolism of sugars by yeast. FEMS Microbiol Rev 32 : 199 224.
111. van Maris AJA, Luttik MAH, Winkler AA, van Dijken JP Pronk JT (2003) Overproduction of threonine aldolase circumvents the biosynthetic role of pyruvate decarboxylase in glucose-limited chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microb 69 : 2094 2099.
112. van Maris AJA, Konings WN, van Dijken JP Pronk JT (2004a) Microbial export of lactic and 3-hydroxypropanoic acid: implications for industrial fermentation processes. Metab Eng 6 : 245 255.
113. van Maris AJA, Winkler AA, Porro D, van Dijken JP Pronk JT (2004b) Homofermentative lactate production cannot sustain anaerobic growth of engineered Saccharomyces cerevisiae: possible consequence of energy-dependent lactate export. Appl Environ Microb 70 : 2898 2905.
114. 2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast. Appl Environ Microb 70 : 159 166.
115. van Maris AJA, Abbott DA, Bellissimi E, van den Brink J, Kuyper M, Luttik MAH, Wisselink HW, Scheffers WA, van Dijken JP Pronk JT (2006) Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces cerevisiae: current status. Antonie van Leeuwenhoek 90 : 391 418.
116. Verduyn C (1991) Physiology of yeasts in relation to biomass yields. Antonie van Leeuwenhoek 60 : 325 353.
117. Verduyn C, Zomerdijk TPL, van Dijken JP Scheffers WA (1984) Continuous measurement of ethanol production by aerobic yeast suspensions with an enzyme electrode. Appl Microbiol Biot 19 : 181 185.
118. Verduyn C, Postma E, Scheffers WA van Dijken JP (1990) Energetics of Saccharomyces cerevisiae in anaerobic glucose-limited chemostat cultures. J Gen Microbiol 136 : 405 412. (Pubitemid 20109731)
119. Verduyn C, Postma E, Scheffers WA van Dijken JP (1992) Effect of benzoic acid on metabolic fluxes in yeast: a continuous-culture study on the regulation of respiration and alcoholic fermentation. Yeast 8 : 501 517.
120. Viegas CA Sá-Correia I (1991) Activation of the plasma membrane ATPase of Saccharomyces cerevisiae by octanoic acid. J Gen Microbiol 137 : 645 651.
121. Vinci V I Byng G S (1999) Strain Improvement by Non-Recombinant Methods. Manual of Industrial Microbiology and Biotechnology, American Society for Microbiology, Washington, DC.
122. Volschenk H, Viljoen M, Grobler J, Petzold B, Bauer F, Subden RE, Young RA, Lonvaud A, Denayrolles M van Vuuren HJJ (1997) Engineering pathways for malate degradation in Saccharomyces cerevisiae. Nat Biotechnol 15 : 253 257.
123. Volschenk H, van Vuuren HJJ Viljoen Bloom M (2003) Malo-ethanolic fermentation in Saccharomyces and Schizosaccharomyces. Curr Genet 43 : 379 391.
124. Walker GM (1998) Yeast Technology. Yeast Physiology and Biotechnology, pp. 265 320. John Wiley & Sons Ltd, Chichester, UK.
125. Warnecke T Gill RT (2005) Organic acid toxicity, tolerance, and production in Escherichia coli biorefining applications. Microb Cell Fact 4 : 25 32.
126. Wei P, Li Z, He P, Lin Y Jiang N (2008) Genome shuffling in the ethanologenic yeast Candida krusei to improve acetic acid tolerance. Biotechnol Appl Bioc 49 : 113 120.
127. Werpy T Petersen G (2004) Top Value Added Chemicals from Biomass: Volume I - Results of Screening for Potential Candidates from Sugars and Synthesis Gas. US Department of Commerce, Springfield, VA. Available at.
128. Zelle RM, de Hulster E, van Winden WA, de Waard P, Dijkema C, Winkler AA, Geertman JM, van Dijken JP, Pronk JT van Maris AJA (2008) Malic acid production by Saccharomyces cerevisiae: engineering of pyruvate carboxylation, oxaloacetate reduction, and malate export. Appl Environ Microb 74 : 2766 2777.