Anaerobic Fermentation for Production of Carboxylic Acids as Bulk Chemicals from Renewable Biomass

  • Jufang Wang
  • Meng Lin
  • Mengmeng Xu
  • Shang-Tian YangEmail author
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 156)


Biomass represents an abundant carbon-neutral renewable resource which can be converted to bulk chemicals to replace petrochemicals. Carboxylic acids have wide applications in the chemical, food, and pharmaceutical industries. This chapter provides an overview of recent advances and challenges in the industrial production of various types of carboxylic acids, including short-chain fatty acids (acetic, propionic, butyric), hydroxy acids (lactic, 3-hydroxypropionic), dicarboxylic acids (succinic, malic, fumaric, itaconic, adipic, muconic, glucaric), and others (acrylic, citric, gluconic, pyruvic) by anaerobic fermentation. For economic production of these carboxylic acids as bulk chemicals, the fermentation process must have a sufficiently high product titer, productivity and yield, and low impurity acid byproducts to compete with their petrochemical counterparts. System metabolic engineering offers the tools needed to develop novel strains that can meet these process requirements for converting biomass feedstock to the desirable product.


Anaerobic fermentation Biomass Bulk chemical Carboxylic acid Metabolic engineering 





3-Hydroxypropionic acid


Acetate kinase


Protocatechuic acid decarboxylase


3-Dehydroshikimic acid dehydratase


Butyrate to acetate ratio


Butyrate kinase


cis-Aconitic acid decarboxylase


Catechol 1,2-dioxygenase


Dissolved oxygen






Formate transporter


Glycerol dehydrogenase


Glycerol dehydratase reactivase


Greenhouse gas


Glycerol facilitator


Glycerol kinase


Hexose monophosphate


Ketoglutaric semialdehyde dehydrogenase


Lactic acid bacteria


Lactate dehydrogenase


Malate dehydrogenase


Methylglyoxal synthase


Methylmalonyl-CoA carboxyltransferase


Methylmalonyl-CoA decarboxylase


Methyl viologen


Oxidoreduction potential


Pyruvate decarboxylase


Pyruvate dehydrogenase




Pyruvate formate lyase


Pyruvate ferredoxin oxidoreductase


Phosphoenolpyruvate carboxylase






NAD+-dependent γ-glutamyl-γ-aminobutyraldehyde dehydrogenase


Pyruvate carboxylase


Reductive tricarboxylic acid


Tricarboxylic acid


NADPH-dependent aldehyde reductase/alcohol dehydrogenase



This work was supported in part by the National Science Foundation STTR program (IIP-1026648), Advanced Research Projects Agency–Energy (DE-AR0000095), the Department of Energy, EERE Bioenergy Technologies Incubator program (DE-EE0007005), and the National Science Foundation of China (21276093).


  1. 1.
    Yang ST, Yu M, Chang WL, Tang IC (2013) Anaerobic fermentations for the production of acetic and butyric acids. In: Yang ST, El-Enshasy HA, Thongchul N (eds) Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers. Wiley, Hoboken, pp 351–373CrossRefGoogle Scholar
  2. 2.
    Ljungdahl LG, Hugenholtz J, Wiegel J (1989) Acetogenic and acid-producing Clostridia. In: Minton NP, Clarke DJ (eds) Clostridia. Plenum, New York, pp 145–180CrossRefGoogle Scholar
  3. 3.
    Parekh SR, Cheryan M (1994) Continuous production of acetate by Clostridium thermoaceticum in a cell-recycle membrane bioreactor. Enzyme Microb Technol 16:104–109CrossRefGoogle Scholar
  4. 4.
    Huang YL, Mann K, Novak JM, Yang ST (1998) Acetic acid production from fructose by Clostridium formicoaceticum in a fibrous-bed bioreactor. Biotechnol Prog 14:800–806CrossRefGoogle Scholar
  5. 5.
    Huang Y, Yang ST (1998) Acetate production from whey lactose using co-immobilized cells of homolactic and homoacetic bacteria in a fibrous-bed bioreactor. Biotechnol Bioeng 60:498–507CrossRefGoogle Scholar
  6. 6.
    Strauba M, Demlerb M, Weuster-Botzb D, Dürre P (2014) Selective enhancement of autotrophic acetate production with genetically modified Acetobacterium woodii. J Biotechnol 178:67–72CrossRefGoogle Scholar
  7. 7.
    Causey TB, Zhou S, Shanmugam KT, Ingram LO (2003) Engineering the metabolism of Escherichia coli W3110 for the conversion of sugar to redox-neutral and oxidized products: homoacetate production. Proc Natl Acad Sci U S A 100:825–832CrossRefGoogle Scholar
  8. 8.
    Samel U-R, Kohler W, Gamer AO, Keuser U, Yang ST, Jin Y, Lin M, Wang Z (2014) Propionic acid and derivatives. In: ULLMANN’S encyclopedia of industrial chemistry. Wiley, Weinheim. doi: 10.1002/14356007.a22_223.pub2
  9. 9.
    Wang Z, Sun J, Zhang A, Yang ST (2013) Propionic acid fermentation. In: Yang ST, El-Enshasy HA, Thongchul N (eds) Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers. Wiley, Hoboken, pp 331–349CrossRefGoogle Scholar
  10. 10.
    Zhang A, Yang ST (2009) Engineering Propionibacterium acidipropionici for enhanced propionic acid tolerance and fermentation. Biotechnol Bioeng 45:79–386Google Scholar
  11. 11.
    Huang YL, Wu Z, Zhang L, Cheung CM, Yang ST (2002) Production of carboxylic acids from hydrolyzed corn meal by immobilized cell fermentation in a fibrous-bed bioreactor. Bioresour Technol 82:51–59CrossRefGoogle Scholar
  12. 12.
    Stowers CC, Cox BM, Rodriguez BA (2014) Development of an industrializable fermentation process for propionic acid production. J Ind Microbiol Biotechnol 41:837–852CrossRefGoogle Scholar
  13. 13.
    Liu Z, Ma C, Gao C, Xu P (2012) Efficient utilization of hemicellulose hydrolysate for propionic acid production using Propionibacterium acidipropionici. Bioresour Technol 114:711–714CrossRefGoogle Scholar
  14. 14.
    Feng X, Chen F, Xu H, Wu B, Li H, Li S, Ouyang P (2011) Green and economical production of propionic acid by Propionibacterium freudenreichii CCTCC M207015 in plant fibrous-bed bioreactor. Bioresour Technol 102:6141–6146CrossRefGoogle Scholar
  15. 15.
    Kagliwal LD, Survase SA, Singhal RS, Granström T (2013) Wheat flour based propionic acid fermentation: an economic approach. Bioresour Technol 129:694–699CrossRefGoogle Scholar
  16. 16.
    Liang Z, Li L, Li S, Cai Y, Yang ST, Wang J (2012) Enhanced propionic acid production from Jerusalem artichoke hydrolysate by immobilized Propionibacterium acidipropionici in a fibrous-bed bioreactor. Bioprocess Biosyst Eng 35:915–921CrossRefGoogle Scholar
  17. 17.
    Zhu L, Wei P, Cai J, Zhu X, Wang Z, Huang L, Xu Z (2012) Improving the productivity of propionic acid with FBB-immobilized cells of an adapted acid-tolerant Propionibacterium acidipropionici. Bioresour Technol 112:248–253CrossRefGoogle Scholar
  18. 18.
    Yang ST, Huang Y, Hong G (1995) A novel recycle batch immobilized cell bioreactor for propionate production from whey lactose. Biotechnol Bioeng 45:379–386CrossRefGoogle Scholar
  19. 19.
    Boyaval P, Corre C (1987) Continuous fermentation of sweet whey permeate for propionic acid production in a CSTR with UF recycle. Biotechnol Lett 9:801–806CrossRefGoogle Scholar
  20. 20.
    Chen F, Feng XH, Liang JF, Xu H, Ouyang PK (2013) An oxidoreduction potential shift control strategy for high purity propionic acid production by Propionibacterium freudenreichii CCTCC M207015 with glycerol as sole carbon source. Bioprocess Biosyst Eng 36:1165–1176CrossRefGoogle Scholar
  21. 21.
    Dishisha T, Alvarez MT, Hatti-Kaul R (2012) Batch and continuous propionic acid production from glycerol using free and immobilized cells of Propionibacterium acidipropionici. Bioresour Technol 118:553–562CrossRefGoogle Scholar
  22. 22.
    Wang Z, Jin Y, Yang ST (2015) High cell density propionic acid fermentation with an acid tolerant strain of Propionibacterium acidipropionici. Biotechnol Bioeng 112:502–511CrossRefGoogle Scholar
  23. 23.
    Dishisha T, Ståhl A, Lundmark S, Hatti-Kaul R (2013) An economical biorefinery process for propionic acid production from glycerol and potato juice using high cell density fermentation. Bioresour Technol 135:504–512CrossRefGoogle Scholar
  24. 24.
    Dishisha T, Ibrahim MH, Cavero VH, Alvarez MT, Hatti-Kaul R (2015) Improved propionic acid production from glycerol: combining cyclic batch and sequential batch fermentations with optimal nutrient composition. Bioresour Technol 176:80–87CrossRefGoogle Scholar
  25. 25.
    Rickert DA, Glatz CE, Glatz BA (1998) Improved organic acid production by calcium alginate-immobilized propionibacteria. Enzyme Microb Technol 22:409–414CrossRefGoogle Scholar
  26. 26.
    Jin Z, Yang ST (1998) Extractive fermentation for enhanced propionic acid production from lactose by Propionibacterium acidipropionici. Biotechnol Prog 14:457–465CrossRefGoogle Scholar
  27. 27.
    Wang P, Wang Y, Liu Y, Shi H, Su Z (2012) Novel in situ product removal technique for simultaneous production of propionic acid and vitamin B12 by expanded bed adsorption bioreactor. Bioresour Technol 104:652–659CrossRefGoogle Scholar
  28. 28.
    Hsu ST, Yang ST (1991) Propionic acid fermentation of lactose by Propionibacterium acidipropionici: effects of pH. Biotechnol Bioeng 38:571–578CrossRefGoogle Scholar
  29. 29.
    Zhuge X, Li J, Shin H, Liu L, Du G, Chen J (2015) Improved propionic acid production with metabolically engineered Propionibacterium jensenii by an oxidoreduction potential-shift control strategy. Bioresour Technol 175:606–612CrossRefGoogle Scholar
  30. 30.
    Emde R, Schink B (1990) Enhanced propionate formation by P. freudenreichii subsp. freudenreichii in a three-electrode amperometric culture system. Appl Environ Microbiol 56:2771–2776Google Scholar
  31. 31.
    Wang P, Jiao Y, Liu S (2014) Novel fermentation process strengthening strategy for production of propionic acid and vitamin B12 by Propionibacterium freudenreichii. J Ind Microbiol Biotechnol 41:1811–1815CrossRefGoogle Scholar
  32. 32.
    Wang Z, Yang ST (2013) Propionic acid production in glycerol/glucose co-fermentation by Propionibacterium freudenreichii subsp. shermanii. Bioresour Technol 137:116–123CrossRefGoogle Scholar
  33. 33.
    Zhang A, Sun J, Wang Z, Yang ST, Zhou H (2015) Effects of carbon dioxide on cell growth and propionic acid production from glycerol and glucose by Propionibacterium acidipropionici. Bioresour Technol 175:374–381CrossRefGoogle Scholar
  34. 34.
    Suwannakham S, Yang ST (2005) Enhanced propionic acid fermentation by Propionibacterium acidipropionici mutant obtained by adaptation in a fibrous-bed bioreactor. Biotechnol Bioeng 91:325–337CrossRefGoogle Scholar
  35. 35.
    Yang ST, Huang H, Tay A, Qin W, De Guzman L, San Nicolas EC (2006) Extractive fermentation for the production of carboxylic acids. In: Yang ST (ed) Bioprocessing for value-added products from renewable resources. Elsevier, Amsterdam, pp 421–446Google Scholar
  36. 36.
    Wόdzki R, Nowaczyk J, Kujawski M (2000) Separation of propionic and acetic acid by pertraction in a multimembrane hybrid system. Sep Purif Technol 21:39–54CrossRefGoogle Scholar
  37. 37.
    Suwannakham S, Huang Y, Yang ST (2006) Construction and characterization of ack knock-out mutants of Propionibacterium acidipropionici for enhanced propionic acid fermentation. Biotechnol Bioeng 94:383–395CrossRefGoogle Scholar
  38. 38.
    Ammar EM, Jin Y, Wang Z, Yang ST (2014) Metabolic engineering of Propionibacterium freudenreichii: effect of expressing phosphoenolpyruvate carboxylase on propionic acid production. Appl Microbiol Biotechnol 98:7761–7772CrossRefGoogle Scholar
  39. 39.
    Parizzi LP, Grassi MC, Llerena LA, Carazzolle MF, Queiroz VL, Lunardi I, Zeidler AF, Teixeira PJPL, Mieczkowski P, Rincones J, Pereira GAG (2012) The genome sequence of Propionibacterium acidipropionici provides insights into its biotechnological and industrial potential. BMC Genomics 13:562CrossRefGoogle Scholar
  40. 40.
    Falentin H, Deutsch SM, Jan G, Loux V, Thierry A, Parayre S, Maillard MB, Dherbécourt J, Cousin FJ, Jardin J, Siguier P, Couloux A, Barbe V, Vacherie B, Wincker P, Gibrat JF, Gaillardin C, Lortal S (2010) The complete genome of Propionibacterium freudenreichii CIRM-BIA1, a hardy actinobacterium with food and probiotic applications. PLoS One 5(7):e11748CrossRefGoogle Scholar
  41. 41.
    Horváth B, Hunyadkürti J, Vörös A, Fekete C, Urbán E, Kemény L, Nagy I (2012) Genome sequence of Propionibacterium acnes type II strain ATCC 11828. J Bacteriol 194:202–203CrossRefGoogle Scholar
  42. 42.
    Wang Z, Ammar EM, Zhang A, Wang L, Lin M, Yang ST (2015) Engineering Propionibacterium freudenreichii subsp. shermanii for enhanced propionic acid fermentation: effects of overexpressing propionyl-CoA:Succinate CoA transferase. Metab Eng 27:46–56CrossRefGoogle Scholar
  43. 43.
    Wang Z, Lin M, Wang L, Ammar EM, Yang ST (2015) Metabolic engineering of Propionibacterium freudenreichii subsp. shermanii for enhanced propionic acid fermentation: effects of overexpressing three biotin-dependent carboxylases. Process Biochem 50:194–204CrossRefGoogle Scholar
  44. 44.
    Zhuge X, Liu L, Shin HD, Chen RR, Li J, Du G, Chen J (2013) Development of a Propionibacterium-Escherichia coli shuttle vector as a useful tool for metabolic engineering of Propionibacterium jensenii, an efficient producer of propionic acid. Appl Environ Microbiol 79:4595–4602CrossRefGoogle Scholar
  45. 45.
    Liu L, Zhuge X, Shin H, Chen RR, Li J, Du G, Chen J (2015) Improved production of propionic acid in Propionibacterium jensenii via combinational overexpression of glycerol dehydrogenase and malate dehydrogenase from Klebsiella pneumoniae. Appl Environ Microbiol 81:2256–2264CrossRefGoogle Scholar
  46. 46.
    Ammar EM, Wang Z, Yang ST (2013) Metabolic engineering of Propionibacterium freudenreichii for n-propanol production. Appl Microbiol Biotechnol 97:4677–4690CrossRefGoogle Scholar
  47. 47.
    Kandasamy V, Vaidyanathan H, Djurdjevic I, Jayamani E, Ramachandran KB, Buckel W, Jayaraman G, Ramalingam S (2013) Engineering Escherichia coli with acrylate pathway genes for propionic acid synthesis and its impact on mixed-acid fermentation. Appl Microbiol Biotechnol 97:1191–1200CrossRefGoogle Scholar
  48. 48.
    Kroschwitz JI (1997) Kirk-Othmer encyclopedia of chemical technology V23: sugar to thin films, 4th edn. Wiley, New York, p 1118Google Scholar
  49. 49.
    Zhang C, Yang H, Yang F, Ma Y (1989) Current progress on butyric acid production by fermentation. Curr Microbiol 59:656–663CrossRefGoogle Scholar
  50. 50.
    Dwidar M, Park JY, Mitchell RJ, Sang BI (2012) The future of butyric acid in industry. Sci World J 2012:471417CrossRefGoogle Scholar
  51. 51.
    Zuo L, Lu M, Zhou Q, Wei W, Wang Y (2013) Butyrate suppresses proliferation and migration of RKO colon cancer cells though regulating endocan expression by MAPK signaling pathway. Food Chem Toxicol 62:892–900CrossRefGoogle Scholar
  52. 52.
    Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ (2008) The role of butyrate on colonic function. Aliment Pharmacol Ther 27:104–119CrossRefGoogle Scholar
  53. 53.
    Canganella F, Kuk SU, Morgan H, Wiegel J (2002) Clostridium thermobutyricum: growth studies and stimulation of butyrate formation by acetate supplementation. Microbiol Res 157:149–156CrossRefGoogle Scholar
  54. 54.
    Tamaru Y, Miyake H, Kuroda K, Nakanishi A, Kawade Y, Yamamoto K, Uemura M, Fujita Y, Doi RH, Ueda M (2010) Genome sequence of the cellulosome-producing mesophilic organism Clostridium cellulovorans 743B. J Bacteriol 192:901–902CrossRefGoogle Scholar
  55. 55.
    Paul D, Austin FW, Arick T, Bridges SM, Burgess SC, Dandass YS, Lawrence ML (2010) Genome sequence of the solvent-producing bacterium Clostridium carboxidivorans strain P7. J Bacteriol 192:5554–5555CrossRefGoogle Scholar
  56. 56.
    Ukpong MN, Atiyeh HK, De Lorme MJ, Liu K, Zhu X, Tanner RS, Wilkins MR, Stevenson BS (2012) Physiological response of Clostridium carboxidivorans during conversion of synthesis gas to solvents in a gas-fed bioreactor. Biotechnol Bioeng 109:2720–2728CrossRefGoogle Scholar
  57. 57.
    Zeikus JG (1980) Chemical and fuel production by anaerobic-bacteria. Annu Rev Microbiol 34:423–464CrossRefGoogle Scholar
  58. 58.
    Zhu Y, Yang ST (2004) Effect of pH on metabolic pathway shift in fermentation of xylose by Clostridium tyrobutyricum. J Biotechnol 110:143–157CrossRefGoogle Scholar
  59. 59.
    Charrier C, Duncan GJ, Reid MD, Rucklidge GJ, Henderson D, Young P, Russell VJ, Aminov RI, Flint HJ, Louis P (2006) A novel class of CoA-transferase involved in short-chain fatty acid metabolism in butyrate-producing human colonic bacteria. Microbiology 152:179–185CrossRefGoogle Scholar
  60. 60.
    Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ (2002) Acetate utilization and butyryl coenzyme A (CoA): acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol 68:5186–5190CrossRefGoogle Scholar
  61. 61.
    Liu X, Zhu Y, Yang ST (2006) Construction and characterization of ack deleted mutant of Clostridium tyrobutyricum for enhanced butyric acid and hydrogen production. Biotechnol Prog 22:1265–1275CrossRefGoogle Scholar
  62. 62.
    Zhu Y, Liu XG, Yang ST (2005) Construction and characterization of pta gene-deleted mutant of Clostridium tyrobutyricum for enhanced butyric acid fermentation. Biotechnol Bioeng 90:154–166CrossRefGoogle Scholar
  63. 63.
    Jang YS, Woo HM, Im JA, Kim IH, Lee SY (2013) Metabolic engineering of Clostridium acetobutylicum for enhanced production of butyric acid. Appl Microbiol Biotechnol 97:9355–9363CrossRefGoogle Scholar
  64. 64.
    Jang YS, Im JA, Choi SY, Lee JI, Lee SY (2014) Metabolic engineering of Clostridium acetobutylicum for butyric acid production with high butyric acid selectivity. Metab Eng 23:165–174CrossRefGoogle Scholar
  65. 65.
    Saini M, Wang ZW, Chiang CJ, Chao YP (2014) Metabolic engineering of Escherichia coli for production of butyric acid. J Agric Food Chem 62:4342–4348CrossRefGoogle Scholar
  66. 66.
    Lim JH, Seo SW, Kim SY, Jung GY (2013) Refactoring redox cofactor regeneration for high-yield biocatalysis of glucose to butyric acid in Escherichia coli. Bioresour Technol 135:568–573CrossRefGoogle Scholar
  67. 67.
    Baek JM, Mazumdar S, Lee SW, Jung MY, Lim JH, Seo SW, Jung GY, Oh MK (2013) Butyrate production in engineered Escherichia coli with synthetic scaffolds. Biotechnol Bioeng 110:2790–2794CrossRefGoogle Scholar
  68. 68.
    Fayolle F, Marchal R, Ballerini D (1990) Effect of controlled substrate feeding on butyric acid production by Clostridium tyrobutyricum. J Ind Microbiol 6:179–183CrossRefGoogle Scholar
  69. 69.
    Huang J, Cai J, Wang J, Zhu X, Huang L, Yang S-T, Xu Z (2011) Efficient production of butyric acid from Jerusalem artichoke by immobilized Clostridium tyrobutyricum in a fibrous-bed bioreactor. Bioresour Technol 102:3923–3926CrossRefGoogle Scholar
  70. 70.
    Jiang L, Wang J, Liang S, Wang X, Cen P, Xu Z (2009) Butyric acid fermentation in a fibrous bed bioreactor with immobilized Clostridium tyrobutyricum from cane molasses. Bioresour Technol 100:3403–3409CrossRefGoogle Scholar
  71. 71.
    Zhu Y, Wu ZT, Yang ST (2002) Butyric acid production from acid hydrolysate of corn fibre by Clostridium tyrobutyricum in a fibrous-bed bioreactor. Process Biochem 38:657–666CrossRefGoogle Scholar
  72. 72.
    Wei D, Liu X, Yang ST (2013) Butyric acid production from sugarcane bagasse hydrolysate by Clostridium tyrobutyricum immobilized in a fibrous-bed bioreactor. Bioresour Technol 129:553–560CrossRefGoogle Scholar
  73. 73.
    Zhu Y, Yang ST (2003) Adaptation of Clostridium tyrobutyricum for enhanced tolerance to butyric acid in a fibrous-bed bioreactor. Biotechnol Prog 19:365–372CrossRefGoogle Scholar
  74. 74.
    Jiang L, Li S, Hu Y, Xu Q, Huang H (2012) Adaptive evolution for fast growth on glucose and the effects on the regulation of glucose transport system in Clostridium tyrobutyricum. Biotechnol Bioeng 109:708–718CrossRefGoogle Scholar
  75. 75.
    Jiang L, Wang J, Liang S, Cai J, Xu Z, Cen P, Yang S, Li S (2011) Enhanced butyric acid tolerance and bioproduction by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor. Biotechnol Bioeng 108:31–40CrossRefGoogle Scholar
  76. 76.
    Zhou X, Lu XH, Li XH, Xin ZJ, Xie JR, Zhao MR, Wang L, Du WY, Liang JP (2014) Radiation induces acid tolerance of Clostridium tyrobutyricum and enhances bioproduction of butyric acid through a metabolic switch. Biotechnol Biofuels 7:22CrossRefGoogle Scholar
  77. 77.
    Michel-Savin D, Marchal R, Vandecasteele JP (1990) Butyric fermentation: metabolic behavior and production performance of Clostridium tyrobutyricum in a continuous culture with cell recycle. Appl Microbiol Biotechnol 34:172–177CrossRefGoogle Scholar
  78. 78.
    Wu ZT, Yang ST (2003) Extractive fermentation for butyric acid production from glucose by Clostridium tyrobutyricum. Biotechnol Bioeng 82:93–102CrossRefGoogle Scholar
  79. 79.
    Du J, Lorenz N, Beitle RR, Hestekin JA (2011) Application of wafer-enhanced electrodeionization in a continuous fermentation process to produce butyric acid with Clostridium tyrobutyricum. Sep Sci Technol 47:43–51CrossRefGoogle Scholar
  80. 80.
    Choi O, Um Y, Sang BI (2012) Butyrate production enhancement by Clostridium tyrobutyricum using electron mediators and a cathodic electron donor. Biotechnol Bioeng 109:2494–2502CrossRefGoogle Scholar
  81. 81.
    Thongchul N (2013) Production of lactic acid and polylactic acid for industrial applications. In: Yang ST, El-Enshasy HA, Thongchul N (eds) Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers. Wiley, Hoboken, pp 293–316CrossRefGoogle Scholar
  82. 82.
    Kascak JS, Kominek J, Roehr M (1996) Lactic acid. In: Rehm H-J, Reed G, Puhler A, Stadler P (eds) Biotechnology, 2nd edn. VCH Verlagsgesellschaft mbH, Weinheim, pp 293–306Google Scholar
  83. 83.
    Kadam SR, Patil SS, Bastawde KB, Khire JA, Gokhale DV (2006) Strain improvement of Lactobacillus delbrueckii NCIM 2365 for lactic acid production. Process Biochem 41:120–126CrossRefGoogle Scholar
  84. 84.
    Benthin S, Villadsen J (1995) Production of optically pure d-lactate by Lactobacillus bulgaricus and purification by crystallization and liquid/liquid extraction. Appl Microbiol Biotechnol 42:426–429CrossRefGoogle Scholar
  85. 85.
    Singh SK, Ahmed SU, Pandey A (2006) Metabolic engineering approaches for lactic acid production. Process Biochem 41:991–1000CrossRefGoogle Scholar
  86. 86.
    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 Microbiol 71:2789–2792CrossRefGoogle Scholar
  87. 87.
    Bianchi MM, Brambilla L, Protani F, Liu CL, Lievense J, Porro D (2001) Efficient homolactic fermentation by Kluyveromyces lactis strains defective in pyruvate utilization and transformed with the heterologous LDH gene. Appl Environ Microbiol 67:5621–5625CrossRefGoogle Scholar
  88. 88.
    Zhou S, Shanmugam KT, Ingram LO (2003) Functional replacement of the Escherichia coli D-(−)-lactate dehydrogenase gene (ldhA) with the L-(+)-lactate dehydrogenase gene (ldhL) from Pediococcus acidilactici. Appl Environ Microbiol 69:2237–2244CrossRefGoogle Scholar
  89. 89.
    Zhou S, Causey TB, Hasona A, Shanmugam KT, Ingram LO (2003) Production of optically pure D-lactic acid in mineral salts medium by metabolically engineered Escherichia coli W3110. Appl Environ Microbiol 69:399–407CrossRefGoogle Scholar
  90. 90.
    Zhu Y, Eiteman MA, DeWitt K, Altman E (2007) Homolactate fermentation by metabolically engineered Escherichia coli strains. Appl Environ Microbiol 73:456–464CrossRefGoogle Scholar
  91. 91.
    Wang L, Zhao B, Li F, Xu K, Ma C, Tao F, Li Q, Xu P (2011) Highly efficient production of D-lactate by Sporolactobacillus sp. CASD with simultaneous enzymatic hydrolysis of peanut meal. Appl Microbiol Biotechnol 89:1009–1017CrossRefGoogle Scholar
  92. 92.
    Okino S, Suda M, Fujikura K, Inui M, Yukawa H (2008) Production of D-lactic acid by Corynebacterium glutamicum under oxygen deprivation. Appl Microbiol Biotechnol 78:449–454CrossRefGoogle Scholar
  93. 93.
    Tay A, Yang ST (2002) Production of L(+)-lactic acid from glucose and starch by immobilized cells of Rhizopus oryzae in a rotating fibrous bed bioreactor. Biotechnol Bioeng 80:1–12CrossRefGoogle Scholar
  94. 94.
    Kumar V, Ashok S, Park S (2013) Recent advances in biological production of 3-hydroxypropionic acid. Biotechnol Adv 31:945–961CrossRefGoogle Scholar
  95. 95.
    Rathnasingh C, Raj SM, Jo JE, Park S (2009) Development and evaluation of efficient recombinant Escherichia coli strains for the production of 3-hydroxypropionic acid from glycerol. Biotechnol Bioeng 104:729–739Google Scholar
  96. 96.
    Jung WS, Kang JH, Chu HS et al (2014) Elevated production of 3-hydroxypropionic acid by metabolic engineering of the glycerol metabolism in Escherichia coli. Metab Eng 23:116–122CrossRefGoogle Scholar
  97. 97.
    Ashok S, Raj SM, Rathnasingh C, Park S (2011) Development of recombinant Klebsiella pneumoniae dhaT strain for the co-production of 3-hydroxypropionic acid and 1,3-propanediol from glycerol. Appl Microbiol Biotechnol 90:1253–1265CrossRefGoogle Scholar
  98. 98.
    Huang Y, Li Z, Shimizu K, Ye Q (2012) Simultaneous production of 3-hydroxypropionic acid and 1,3-propanediol from glycerol by a recombinant strain of Klebsiella pneumoniae. Bioresour Technol 103:351–359CrossRefGoogle Scholar
  99. 99.
    Ashok S, Sankaranarayanan M, Ko Y, Jae KE, Ainala SK, Kumar V, Park S (2013) Production of 3-hydroxypropionic acid from glycerol by recombinant Klebsiella pneumoniae ΔdhaTΔyqhD which can produce vitamin B12 naturally. Biotechnol Bioeng 110:511–524CrossRefGoogle Scholar
  100. 100.
    Quispe CAG, Coronado CJR, Carvalho JA Jr (2013) Glycerol: production, consumption, prices, characterization and new trends in combustion. Renew Sustain Energy Rev 27:475–493CrossRefGoogle Scholar
  101. 101.
    Yi J, Choi S, Han M-S, Lee JW, Lee SY (2013) Production of succinic acid from renewable resources. In: Yang ST, El-Enshasy HA, Thongchul N (eds) Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers. Wiley, Hoboken, pp 317–330CrossRefGoogle Scholar
  102. 102.
    Zeikus JG, Jain MK, Elankovan P (1999) Biotechnology of succinic acid production and markets for derived industrial products. Appl Microbiol Biotechnol 51:545–552CrossRefGoogle Scholar
  103. 103.
    Lee PC, Lee WG, Lee SY, Chang HN (2001) Succinic acid production with reduced by-product formation in the fermentation of Anaerobiospirillum succiniciproducens using glycerol as a carbon source. Biotechnol Bioeng 72:41–48CrossRefGoogle Scholar
  104. 104.
    Lee SJ, Song H, Lee SY (2006) Genome-based metabolic engineering of Mannheimia succiniciproducens for succinic acid production. Appl Environ Microbiol 72:1939–1948CrossRefGoogle Scholar
  105. 105.
    Glassner DA, Datta R (1992) Process for the production and purification of succinic acid. US Patent 5,143,834Google Scholar
  106. 106.
    Meynial-Salles I, Dorotyn S, Soucaille P (2008) A new process for the continuous production of succinic acid from glucose at high yield, titer, and productivity. Biotechnol Bioeng 99:129–135CrossRefGoogle Scholar
  107. 107.
    Guettler MV, Jain MK, Soni BK (1998) Process for making succinic acid, microorganisms for use in the process and methods of obtaining the microorganisms. US Patent 5,723,322Google Scholar
  108. 108.
    Guettler MV, Jain MK, Rumler D (1996) Method for making succinic acid, bacterial variants for use in process, and methods for obtaining variants. US Patent 5,573,931Google Scholar
  109. 109.
    Park DH, Laivenieks M, Guettler MV, Jain MK, Zeikus JG (1999) Microbial utilization of electrically reduced neutral red as the sole electron donor for growth and metabolite production. Appl Environ Microbiol 65:2912–2917Google Scholar
  110. 110.
    Song H, Kim TY, Choi BK, Choi SJ, Nielsen LK, Chang HN, Lee SY (2008) Development of chemically defined medium for Mannheimia succiniciproducens based on its genome sequence. Appl Microbiol Biotechnol 79:263–272CrossRefGoogle Scholar
  111. 111.
    Kim P, Laivenieks M, Vieille C, Zeikus JG (2004) Effect of overexpression of Actinobacillus succinogenes phosphoenolpyruvate carboxykinase on succinate production in Escherichia coli. Appl Environ Microbiol 70:1238–1241CrossRefGoogle Scholar
  112. 112.
    Kim TY, Kim HU, Park JM, Song H, Kim JS, Lee SY (2007) Genome-scale analysis of Mannheimia succiniciproducens metabolism. Biotechnol Bioeng 97:657–671CrossRefGoogle Scholar
  113. 113.
    Okino S, Noburyu R, Suda M, Jojima T, Inui M, Yukawa H (2008) An efficient succinic acid production process in a metabolically engineered Corynebacterium glutamicum strain. Appl Microbiol Biotechnol 81:459–464CrossRefGoogle Scholar
  114. 114.
    Hong SH (2007) Systems approaches to succinic acid-producing microorganisms. Biotechnol Bioprocess Eng 12:73–79CrossRefGoogle Scholar
  115. 115.
    YangST LX, Zhang Y (2007) Metabolic engineering – applications, methods, and challenges. In: Yang ST (ed) Bioprocessing for value-added products from renewable resources: new technologies and applications. Elsevier, Amsterdam, pp 73–118Google Scholar
  116. 116.
    Jantama K, Zhang X, Moore JC, Shanmugam KT, Svoronos SA, Ingram LO (2008) Eliminating side products and increasing succinate yields in engineered strains of Escherichia coli C. Biotechnol Bioeng 101:881–893CrossRefGoogle Scholar
  117. 117.
    Vemuri GN, Eiteman MA, Altman E (2002) Succinate production in dual-phase Escherichia coli fermentations depends on the time of transition from aerobic to anaerobic conditions. J Ind Microbiol Biotechnol 28:325–332CrossRefGoogle Scholar
  118. 118.
    Vemuri GN, Eiteman MA, Altman E (2002) Effects of growth mode and pyruvate carboxylase on succinic acid production by metabolically engineered strains of Escherichia coli. Appl Environ Microbiol 68:1715–1727CrossRefGoogle Scholar
  119. 119.
    Lin H, Bennett GN, San K-Y (2005) Effect of carbon sources differing in oxidation state and transport route on succinate production in metabolically engineered Escherichia coli. J Ind Microbiol Biotechnol 32:87–93CrossRefGoogle Scholar
  120. 120.
    San K-Y, Bennett GN, Berríos-Rivera SJ, Vadali RV, Yang Y-T, Horton E, Rudolph FB, Sariyar B, Blackwood K (2002) Metabolic engineering through cofactor manipulation and its effects on metabolic flux redistribution in Escherichia coli. Metab Eng 4:182–192CrossRefGoogle Scholar
  121. 121.
    Thakker C, Martínez I, San K-Y, Bennett GN (2012) Succinate production in Escherichia coli. Biotechnol J 7(2):213–224CrossRefGoogle Scholar
  122. 122.
    Otero JM, Cimini D, Patil KR, Poulsen SG, Olsson L, Nielsen J (2013) Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory. PLoS One 8(1):e54144CrossRefGoogle Scholar
  123. 123.
    Yan D, Wang C, Zhou J, Liu Y, Yang M, Xing J (2014) Construction of reductive pathway in Saccharomyces cerevisiae for effective succinic acid fermentation at low pH value. Bioresour Technol 156:232–239CrossRefGoogle Scholar
  124. 124.
    Zhang K, Zhang B, Yang ST (2013) Production of citric, itaconic, fumaric and malic acids in filamentous fungal fermentations. In: Yang ST, El-Enshasy HA, Thongchul N (eds) Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers. Wiley, Hoboken, pp 375–397CrossRefGoogle Scholar
  125. 125.
    Battat E, Peleg Y, Bercovitz A, Rokem JS, Goldberg I (1991) Optimization of L-malic acid production by Aspergillus flavus in a stirred fermentor. Biotechnol Bioeng 37:1108–1116CrossRefGoogle Scholar
  126. 126.
    Taing O, Taing K (2007) Production of malic and succinic acids by sugar-tolerant yeast Zygosaccharomyces rouxii. Eur Food ResTechnol 224:343–347CrossRefGoogle Scholar
  127. 127.
    West TP (2011) Malic acid production from thin stillage by Aspergillus species. Biotechnol Lett 33:2463–2467CrossRefGoogle Scholar
  128. 128.
    Lumyong S, Tomita F (1993) L-malic acid production by an albino strain Monascus araneosus. World J Microbiol Biotechnol 9:383–384CrossRefGoogle Scholar
  129. 129.
    Kawagoe M, Hyakumura K, Suye SI, Miki K, Naoe K (1997) Application of bubble column fermenters to submerged culture of Schizophyllum commune for production of L-malic acid. J Ferment Bioeng 84:333–336CrossRefGoogle Scholar
  130. 130.
    Liu SJ, Steinbuchel A (1997) Production of poly(malic acid) from different carbon sources and its regulation in Aureobasidium pullulans. Biotechnol Lett 19:11–14CrossRefGoogle Scholar
  131. 131.
    Zou X, Zhou YP, Yang ST (2013) Production of polymalic acid and malic acid by Aureobasidium pullulans fermentation and acid hydrolysis. Biotechnol Bioeng 110:2105–2113CrossRefGoogle Scholar
  132. 132.
    Brown SH, Bashkirova L, Berka R, Chandler T, Doty T, McCall K et al (2013) Metabolic engineering of Aspergillus oryzae NRRL 3488 for increased production of L-malic acid. Appl Microbiol Biotechnol 97:8903–8912CrossRefGoogle Scholar
  133. 133.
    Zelle RM, de Hulster E, van Winden WA, de Waard P, Dijkema C, Winkler AA et al (2008) Malic acid production by Saccharomyces cerevisiae: engineering of pyruvate carboxylation, oxaloacetate reduction, and malate export. Appl Environ Microbiol 74:2766–2777CrossRefGoogle Scholar
  134. 134.
    Moon SY, Hong SH, Kim TY, Lee SY (2008) Metabolic engineering of Escherichia coli for the production of malic acid. Biochem Eng J 40:312–320CrossRefGoogle Scholar
  135. 135.
    Jantama K, Haupt MJ, Svoronos SA, Zhang XL, Moore JC, Shanmugam KT, Ingram LO (2008) Combining metabolic engineering and metabolic evolution to develop nonrecombinant strains of Escherichia coli C that produce succinate and malate. Biotechnol Bioeng 99:1140–1153CrossRefGoogle Scholar
  136. 136.
    Zhang X, Wang X, Shanmugam KT, Ingram LO (2011) L-Malate production by metabolically engineered Escherichia coli. Appl Environ Microbiol 77:427–434CrossRefGoogle Scholar
  137. 137.
    Yang ST, Zhang K, Zhang B, Huang H (2011) Bio-based chemicals - fumaric acid. In: Moo-Young M (ed) Comprehensive biotechnology, vol 3, 2nd edn. Elsevier, Burlington, pp 163–177CrossRefGoogle Scholar
  138. 138.
    Xu Q, Li S, Huang H, Wen J (2012) Key technologies for the industrial production of fumaric acid by fermentation. Biotechnol Adv 30:1685–1696CrossRefGoogle Scholar
  139. 139.
    Xu G, Chen X, Liu L, Jiang L (2013) Fumaric acid production in Saccharomyces cerevisiae by simultaneous use of oxidative and reductive routes. Bioresour Technol 148:91–96CrossRefGoogle Scholar
  140. 140.
    Ling LB, Ng TK (1989) Fermentation process for carboxylic acids. US 4,877,731Google Scholar
  141. 141.
    Cao NJ, Du JX, Gong CS, Tsao GT (1996) Simultaneous production and recovery of fumaric acid from immobilized Rhizopus oryzae with a rotary biofilm contactor and an adsorption column. Appl Environ Microbiol 62:2926–2931Google Scholar
  142. 142.
    Das RK, Brar SK (2014) Enhanced fumaric acid production from brewery wastewater and insight into the morphology of Rhizopus oryzae 1526. Appl Biochem Biotechnol 172:2974–2988CrossRefGoogle Scholar
  143. 143.
    Zhou Y, Nie K, Zhang X, Liu S, Wang M, Deng L et al (2014) Production of fumaric acid from biodiesel-derived crude glycerol by Rhizopus arrhizus. Bioresour Technol 163:48–53CrossRefGoogle Scholar
  144. 144.
    Zhang BH, Yang ST (2012) Metabolic engineering of Rhizopus oryzae: effects of overexpressing fumR gene on cell growth and fumaric acid biosynthesis from glucose. Process Biochem 47:2159–2165CrossRefGoogle Scholar
  145. 145.
    Zhang BH, Skory CD, Yang ST (2012) Metabolic engineering of Rhizopus oryzae: effects of overexpressing pyc and pepc genes on fumaric acid biosynthesis from glucose. Metab Eng 14:512–520CrossRefGoogle Scholar
  146. 146.
    Song CW, Kim DI, Choi S, Jang JW, Lee SY (2013) Metabolic engineering of Escherichia coli for the production of fumaric acid. Biotechnol Bioeng 110:2025–2034CrossRefGoogle Scholar
  147. 147.
    Chen X, Wu J, Song W, Zhang L, Wang H, Liu L (2015) Fumaric acid production by Torulopsis glabrata: engineering the urea cycle and the purine nucleotide cycle. Biotechnol Bioeng 112:156–167CrossRefGoogle Scholar
  148. 148.
    Okabe M, Lies D, Kanamasa S, Park EY (2009) Biotechnological production of itaconic acid and its biosynthesis in Aspergillus terreus. Appl Microbiol Biotechnol 84:597–606CrossRefGoogle Scholar
  149. 149.
    Yahiro K, Takahama T, Park YS, Okabe M (1995) Breeding of Aspergillus terreus mutant Tn-484 for itaconic acid production with high-yield. J Ferment Bioeng 79:506–508CrossRefGoogle Scholar
  150. 150.
    Kawamura D, Furuhashi M, Saito O, Matsui H (1981) Production of itaconic acid by fermentation. Japan Patent 56,137,893Google Scholar
  151. 151.
    Blazeck J, Miller J, Pan A, Gengler J, Holden C, Jamoussi M, Alper HS (2014) Metabolic engineering of Saccharomyces cerevisiae for itaconic acid production. Appl Microbiol Biotechnol 98:8155–8164CrossRefGoogle Scholar
  152. 152.
    Blazeck J, Hill A, Jamoussi M, Pan A, Miller J, Alper HS (2015) Metabolic engineering of Yarrowia lipolytica for itaconic acid production. Metab Eng 32:66–73CrossRefGoogle Scholar
  153. 153.
    Polen T, Spelberg M, Bott M (2012) Toward biotechnological production of adipic acid and precursors from biorenewables. J Biotechnol 167:75–84CrossRefGoogle Scholar
  154. 154.
    Yu J-L, Xia X-X, Zhong J-J, Qian Z-G (2014) Direct biosynthesis of adipic acid from a synthetic pathway in recombinant Escherichia coli. Biotechnol Bioeng 111:2580–2586CrossRefGoogle Scholar
  155. 155.
    Niu W, Draths KM, Frost JW (2002) Benzene-free synthesis of adipic acid. Biotechnol Prog 18:201–211CrossRefGoogle Scholar
  156. 156.
    Moon TS, Yoon SH, Lanza AM, Roy-Mayhew JD, Prather KLJ (2009) Production of glucaric acid from a synthetic pathway in recombinant Escherichia coli. Appl Environ Microbiol 75:589–595CrossRefGoogle Scholar
  157. 157.
    Moon TS, Dueber JE, Shiue E, Prather KLJ (2010) Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli. Metab Eng 12:298–305CrossRefGoogle Scholar
  158. 158.
    Straathof AJJ, Sie S, Franco TT, van der Wielen LAM (2005) Feasibility of acrylic acid production by fermentation. Appl Microbiol Biotechnol 67:727–734CrossRefGoogle Scholar
  159. 159.
    Ishii M, Chuakrut S, Arai H, Igarashi Y (2004) Occurrence, biochemistry and possible biotechnological application of the 3-hydroxypropionate cycle. Appl Microbiol Biotechnol 64:605–610CrossRefGoogle Scholar
  160. 160.
    Li Y, Chen J, Lun S-Y (2001) Biotechnological production of pyruvic acid. Appl Microbiol Biotechnol 57:451–459CrossRefGoogle Scholar
  161. 161.
    Miyata R, Yonehara T (1999) Breeding of high-pyruvate-producing Torulopsis glabrata with acquired reduced pyruvate decarboxylase. J Biosci Bioeng 88:173–178CrossRefGoogle Scholar
  162. 162.
    Wieschalka S, Blombach B, Eikmanns BJ (2012) Engineering Corynebacterium glutamicum for the production of pyruvate. Appl Microbiol Biotechnol 94:449–459CrossRefGoogle Scholar
  163. 163.
    Zhu Y, Eiteman MA, Altman R, Altman E (2008) High glycolytic flux improves pyruvate production by a metabolically engineered Escherichia coli strain. Appl Environ Microbiol 74:6649–6655CrossRefGoogle Scholar
  164. 164.
    Maris AJ, Geertman JM, Vermeulen A, Groothuizen MK, Winkler AA, Piper MDW, Van Dijken JP, Pronk JT (2004) Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae, yielding a C2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast. Appl Environ Microbiol 70:159–166CrossRefGoogle Scholar
  165. 165.
    Roehr M, Kubicek CP, Kominek J (1996) Citric acid. In: Roehr M (ed) Biotechnology, vol 6, 2nd edn, Products of primary metabolism. Verlag Chemie, Weinheim, pp 308–345Google Scholar
  166. 166.
    Max B, Salgado JM, Rodriguez N, Cortes S, Converti A, Dominguez JM (2010) Biotechnological production of citric acid. Braz J Microbiol 41:862–875CrossRefGoogle Scholar
  167. 167.
    Anastassiadis S, Rehm HJ (2006) Citric acid production from glucose by yeast Candida oleophila ATCC 20177 under batch, continuous and repeated batch cultivation. Electron J Biotechnol 9:26–39CrossRefGoogle Scholar
  168. 168.
    Rywinska A, Rymowicz W, Larowska B, Wojtatowicz M (2009) Biosynthesis of citric acid from glycerol by acetate mutants of Yarrowia lipolytica in fed-batch fermentation. Food Technol Biotechnol 47:1–6Google Scholar
  169. 169.
    Forster A, Aurich A, Mauersberger S, Barth G (2007) Citric acid production from sucrose using a recombinant strain of the yeast Yarrowia lipolytica. Appl Microbiol Biotechnol 75:1409–1417CrossRefGoogle Scholar
  170. 170.
    Liu XY, Chi Z, Liu GL, Madzak C, Chi ZM (2013) Both decrease in ACL1 gene expression and increase in ICL1 gene expression in marine-derived yeast Yarrowia lipolytica expressing INU1 gene enhance citric acid production from inulin. Mar Biotechnol 15:26–36CrossRefGoogle Scholar
  171. 171.
    Roehr M, Kubicek CP, Kominek J (1996) Gluconic acid. In: Roehr M (ed) Biotechnology, vol 6, 2nd edn, Products of Primary Metabolism. Verlag Chemie, Weinheim, pp 347–362CrossRefGoogle Scholar
  172. 172.
    Anastassiadis S, Aivasidis A, Wandrey C (2003) Continuous gluconic acid production by isolated yeast-like mould strains of Aureobasidium pullulans. Appl Microbiol Biotechnol 61:110–117CrossRefGoogle Scholar
  173. 173.
    Yin X, Li J, Shin H-D, Du G, Liu L, Chen J (2015) Metabolic engineering in the biotechnological production of organic acids in the tricarboxylic acid cycle of microorganisms: advances and prospects. Biotechnol Adv 33:830–841CrossRefGoogle Scholar
  174. 174.
    Sun J, Alper HS (2015) Metabolic engineering of strains: from industrial-scale to lab-scale chemical production. J Ind Microbiol Biotechnol 42:423–436CrossRefGoogle Scholar
  175. 175.
    Jang Y-S, Kim B, Shin JH, Choi YJ, Choi S, Song CW, Lee J, Park HG, Lee SY (2012) Bio-based production of C2–C6 platform chemicals. Biotechnol Bioeng 109:2437–2459CrossRefGoogle Scholar
  176. 176.
    Lee JW, Kim HU, Choi S, Yi J, Lee SY (2011) Microbial production of building block chemicals and polymers. Curr Opin Biotechnol 22:758–767CrossRefGoogle Scholar
  177. 177.
    Shin JH, Kim HU, Kim DI, Lee SY (2013) Production of bulk chemicals via novel metabolic pathways in microorganisms. Biotechnol Adv 31:925–935CrossRefGoogle Scholar
  178. 178.
    Karaffa L, Kubicek CP (2003) Aspergillus niger citric acid accumulation: do we understand this well working black box? Appl Microbiol Biotechnol 61:189–196CrossRefGoogle Scholar
  179. 179.
    Nicolaou SA, Gaida SM, Papoutsakis ET (2010) A comparative view of metabolite and substrate stress and tolerance in microbial bioprocessing: from biofuels and chemicals, to biocatalysis and bioremediation. Metab Eng 12:307–331CrossRefGoogle Scholar
  180. 180.
    Xu M, Zhao J, Yu L, Tang I-C, Xue C, Yang ST (2015) Engineering Clostridium acetobutylicum with a histidine kinase knockout for enhanced n-butanol tolerance and production. Appl Microbiol Biotechnol 99:1011–1022CrossRefGoogle Scholar
  181. 181.
    Royce LA, Yoon JM, Chen Y, Rickenbach E, Shanks JV, Jarboe LR (2015) Evolution for exogenous octanoic acid tolerance improves carboxylic acid production and membrane integrity. Metab Eng 29:180–188CrossRefGoogle Scholar
  182. 182.
    Yang ST, Lu C (2013) Extraction-fermentation hybrid (extractive fermentation). In: Ramaswamy S, Ramarao BV, Huang H (eds) Separation and purification technologies in biorefineries. Wiley, Chichester, pp 409–437CrossRefGoogle Scholar
  183. 183.
    Du Y, Jiang W, Yu M, Tang I-C, Yang S-T (2015) Metabolic process engineering of Clostridium tyrobutyricum Δack-adhE2 for enhanced n-butanol production from glucose: effects of methyl viologen on NADH availability, flux distribution and fermentation kinetics. Biotechnol Bioeng 112:705–715CrossRefGoogle Scholar
  184. 184.
    Parisutham V, Kim TH, Lee SK (2014) Feasibilities of consolidated bioprocessing microbes: from pretreatment to biofuel production. Bioresour Technol 161:431–440CrossRefGoogle Scholar
  185. 185.
    Yang ST, Yu M (2013) Integrated biorefinery for sustainable production of fuels, chemicals and polymers. In: Yang ST, El-Enshasy HA, Thongchul N (eds) Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers. Wiley, Hoboken, pp 1–26CrossRefGoogle Scholar
  186. 186.
    Almeida JRM, Fávaro LCL, Quirino BF (2012) Biodiesel biorefinery: opportunities and challenges for microbial production of fuels and chemicals from glycerol waste. Biotechnol Biofuels 5:48CrossRefGoogle Scholar
  187. 187.
    Anand P, Saxena RK (2012) A comparative study of solvent-assisted pretreatment of biodiesel derived crude glycerol on growth and 1,3-propanediol production from Citrobacter freundi. N Biotechnol 29:199–205CrossRefGoogle Scholar
  188. 188.
    Schiel-Bengelsdorf B, Durre P (2012) Pathway engineering and synthetic biology using acetogens. FEBS Lett 586:2191–2198CrossRefGoogle Scholar
  189. 189.
    Fast AG, Papoutsakis ET (2012) Stoichiometric and energetic analyses of non-photosynthetic CO2-fixation pathways to support synthetic biology strategies for production of fuels and chemicals. Curr Opin Chem Eng 1:380–395CrossRefGoogle Scholar
  190. 190.
    Munasinghe PC, Khanal SK (2010) Biomass-derived syngas fermentation into biofuels: opportunities and challenges. Bioresour Technol 101:5013–5022CrossRefGoogle Scholar
  191. 191.
    Wang J, Yang X, Chen C-C, Yang ST (2014) Engineering clostridia for butanol production from biorenewable resources: from cells to process integration. Curr Opin Chem Eng 6:43–54CrossRefGoogle Scholar
  192. 192.
    Jang Y-S, Park JM, Choi S, Choi YJ, Seung DY, Cho JH, Lee SY (2012) Engineering of microorganisms for the production of biofuels and perspectives based on systems metabolic engineering approaches. Biotechnol Adv 30:989–1000CrossRefGoogle Scholar
  193. 193.
    Lee JW, Na D, Park JM, Lee J, Choi S, Lee SY (2012) Systems metabolic engineering of microorganisms for natural and non-natural chemicals. Nat Chem Biol 8:536–546CrossRefGoogle Scholar
  194. 194.
    Seo SW, Yang J, Min BE, Jang S, Lim JH, Lim HG, Kim SC, Kim SY, Jeong JH, Jung GY (2013) Synthetic biology: tools to design microbes for the production of chemicals and fuels. Biotechnol Adv 31:811–817CrossRefGoogle Scholar
  195. 195.
    Jullesson D, David F, Pfleger B, Nielsen J (2015) Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals. Biotechnol Adv. doi: 10.1016/j.biotechadv.2015.02.011 (in press)
  196. 196.
    McNerney MP, Watstein DM, Styczynski MP (2015) Precision metabolic engineering: the design of responsive, selective, and controllable metabolic systems. Metab Eng 31:123–131CrossRefGoogle Scholar
  197. 197.
    Yu C, Cao Y, Zou H, Xian M (2011) Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols. Appl Microbiol Biotechnol 89:573–583CrossRefGoogle Scholar
  198. 198.
    Borodina I, Nielsen J (2014) Advances in metabolic engineering of yeast Saccharomyces cerevisiae for production of chemicals. Biotechnol J 9:609–620CrossRefGoogle Scholar
  199. 199.
    Wieschalka S, Blombach B, Bott M, Eikmanns BJ (2013) Bio-based production of organic acids with Corynebacterium glutamicum. Microb Biotechnol 6:87–102CrossRefGoogle Scholar
  200. 200.
    Tracy BP, Jones SW, Fast AG, Indurthi DC, Papoutsakis ET (2012) Clostridia: the importance of their exceptional substrate and metabolite diversity for biofuel and biorefinery applications. Curr Opin Biotechnol 23:364–381CrossRefGoogle Scholar
  201. 201.
    Yu M, Du Y, Jiang W, Chang W-L, Yang ST, Tang I-C (2012) Effects of different replicons in conjugative plasmids on transformation efficiency, plasmid stability, gene expression and n-butanol biosynthesis in Clostridium tyrobutyricum. Appl Microbiol Biotechnol 93:881–889CrossRefGoogle Scholar
  202. 202.
    Yu M, Zhang Y, Tang IC, Yang ST (2011) Metabolic engineering of Clostridium tyrobutyricum for n-butanol production. Metab Eng 13:373–382CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Jufang Wang
    • 1
    • 2
  • Meng Lin
    • 3
  • Mengmeng Xu
    • 2
  • Shang-Tian Yang
    • 2
    Email author
  1. 1.School of Bioscience and BioengineeringSouth China University of TechnologyGuangzhouP.R. China
  2. 2.William G. Lowrie Department of Chemical and Biomolecular EngineeringThe Ohio State UniversityColumbusUSA
  3. 3.Bioprocessing Innovative CompanyDublinUSA

Personalised recommendations