Bioproduction of Chemicals: An Introduction

  • Yokimiko David
  • Mary Grace Baylon
  • Sang Yup Lee
  • Si Jae Park
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


The successful transition of a petroleum-based economy to a more sustainable economy is highly dependent on the development of technologies that will meet the demands for the production of fuel and industrially important chemicals. Establishment of microorganism-based biorefineries is a promising route in realizing this goal through the application of metabolically engineered microorganisms capable of converting renewable biomasses to value-added chemicals. This review encompasses the constructed synthetic pathways and microbial strain improvement strategies developed to date for the direct production of building-block chemicals from renewable biomass.



This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea (NRF-2015M1A2A2035810) and Mid-career Researcher Program through NRF grant funded by the MSIT (NRF-2016R1A2B4008707).


  1. Abdel-Rahman MA, Xiao Y, Tashiro Y, Wang Y, Zendo T, Sakai K, Sonomoto K (2015) Fed-batch fermentation for enhanced lactic acid production from glucose/xylose mixture without carbon catabolite repression. J Biosci Bioeng 119(2):153–158CrossRefPubMedGoogle Scholar
  2. Ahn JH, Jang YS, Lee SY (2016) Production of succinic acid by metabolically engineered microorganisms. Curr Opin Biotechnol 42:54–66CrossRefPubMedGoogle Scholar
  3. Beauprez JJ, De Mey M, Soetaert WK (2010) Microbial succinic acid production: natural versus metabolic engineered producers. Process Biochem 45:1103–1114CrossRefGoogle Scholar
  4. Biddy MJ, Scarlata C, Kinchin C (2016) Chemicals from biomass: a market assessment of bioproducts with near-term potential (No. NREL/TP-5100-65509). NREL (National Renewable Energy Laboratory (NREL), Golden, COGoogle Scholar
  5. Cammas S, Renard I, Langlois V, Guéri P (1996) Poly (β-malic acid): obtaining high molecular weights by improvement of the synthesis route. Polymer 37:4215–4220CrossRefGoogle Scholar
  6. Celińska E, Grajek W (2009) Biotechnological production of 2, 3-butanediol – current state and prospects. Biotechnol Adv 27:715–725CrossRefPubMedGoogle Scholar
  7. Cheng K, Zhao X, Zeng J, Zhang (2012) Biotechnological production of succinic acid: current state and perspectives. Biofuel Bioprod Bior 6:302–318Google Scholar
  8. Cheng Z, Jiang J, Wu H, Li Z, Ye Q (2016) Enhanced production of 3-hydroxypropionic acid from glucose via malonyl-CoA pathway by engineered Escherichia coli. Bioresour Technol 200:897–904CrossRefPubMedGoogle Scholar
  9. Choi S, Song H, Lim SW, Kim TY, Ahn JH, Lee JW, Lee MH, Lee SY (2016) Highly selective production of succinic acid by metabolically engineered Mannheimia succiniciproducens and its efficient purification. Biotechnol BioengGoogle Scholar
  10. Chu HS, Kim YS, Lee CM, Lee JH, Jung WS, Ahn JH, Song SH, Choi IS, Cho KM (2015) Metabolic engineering of 3-hydroxypropionic acid biosynthesis in Escherichia coli. Biotechnol Bioeng 112:356–364CrossRefPubMedGoogle Scholar
  11. Ge Y, Li K, Li L, Gao C, Zhang L, Ma C, Xu P (2016) Contracted but effective: production of enantiopure 2,3-butanediol by thermophilic and GRAS Bacillus licheniformis. Green Chem 18:4693–4703CrossRefGoogle Scholar
  12. Grabar TB, Zhou S, Shanmugam KT, Yomano LP, Ingram LO (2006) Methylglyoxal bypass identified as source of chiral contamination in L(+) and D(−)-lactate fermentations by recombinant Escherichia coli. Biotechnol Lett 28:1527–1535CrossRefPubMedGoogle Scholar
  13. Ji XJ, Huang H, Ouyang PK (2011) Microbial 2, 3-butanediol production: a state-of-the-art review. Biotechnol Adv 29:351–364CrossRefPubMedGoogle Scholar
  14. Jung YK, Kim TY, Park SJ, Lee SY (2010) Metabolic engineering of Escherichia coli for the production of polylactic acid and its copolymers. Biotechnol Bioeng 105:161–171CrossRefPubMedGoogle Scholar
  15. Jung IY, Lee JW, Min WK, Park YC, Seo JH (2015) Simultaneous conversion of glucose and xylose to 3-hydroxypropionic acid in engineered Escherichia coli by modulation of sugar transport and glycerol synthesis. Bioresour Technol 198:709–716CrossRefPubMedGoogle Scholar
  16. Kataoka N, Vangnai AS, Tajima T, Nakashimada Y, Kato J (2013) Improvement of (R)-1,3-butanediol production by engineered Escherichia coli. J Biosci Bioeng 115:475–480CrossRefPubMedGoogle Scholar
  17. Kataoka N, Vangnai AS, Ueda H, Tajima T, Nakashimada Y, Kato J (2014) Enhancement of (R)-1,3-butanediol production by engineered Escherichia coli using a bioreactor system with strict regulation of overall oxygen transfer coefficient and pH. Biosci Biotechnol Biochem 78:695–700CrossRefPubMedGoogle Scholar
  18. Kumar V, Ashok S, Park S (2013) Recent advances in biological production of 3-hydroxypropionic acid. Biotechnoll adv 31:945–961CrossRefGoogle Scholar
  19. Lee HK, Maddox IS (1986) Continuous production of 2, 3-butanediol from whey permeate using Klebsiella pneumoniae immobilized in calcium alginate. Enzym Microb Technol 8:409–411CrossRefGoogle Scholar
  20. Li Y, Wang X, Ge X, Tian P (2016) High production of 3-hydroxypropionic acid in Klebsiella pneumoniae by systematic optimization of glycerol metabolism. Sci Rep 6:26932CrossRefPubMedPubMedCentralGoogle Scholar
  21. Lim HG, Noh MH, Jeong JH, Park S, Jung GY (2016) Optimum rebalancing of the 3-hydroxypropionic acid production pathway from glycerol in Escherichia coli. ACS Synth Biol 5(11):1247–1255CrossRefPubMedGoogle Scholar
  22. Liu H, Lu T (2015) Autonomous production of 1,4-butanediol via de novo biosynthesis pathway in engineered Escherichia coli. Metab Eng 29:135–141CrossRefPubMedGoogle Scholar
  23. Luo H, Zhou D, Liu X, Nie Z, Quiroga-Sánchez DL, Chang Y (2016) Production of 3-Hydroxypropionic acid via the propionyl-coa pathway using recombinant Escherichia coli strains. PLoS One 11:e0156286CrossRefPubMedPubMedCentralGoogle Scholar
  24. Matsuyama A, Yamamoto H, Kawada N, Kobayashi Y (2001) Industrial production of (R)-1,3-butanediol by new biocatalysts. J Mol Catal B Enzym 11:513–521CrossRefGoogle Scholar
  25. Meng Y, Xue Y, Yu B, Gao C, Ma Y (2012) Efficient production of L-lactic acid with high optical purity by alkaliphilic Bacillus sp. WL-S20. Bioresour Technol 116:334–339CrossRefPubMedGoogle Scholar
  26. 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
  27. Oh YH, Eom IY, Joo JC, Yu JH, Song BK, Lee SH, Hong SH, Park SJ (2015) Recent advances in development of biomass pretreatment technologies used in biorefinery for the production of bio-based fuels, chemicals and polymers. Korean J Chem Eng 32:1945–1959CrossRefGoogle Scholar
  28. Park JM, Hong WK, Lee SM, Heo SY, Jung YR, Kang IY, BR O, Seo JW, Kim CH (2014) Identification and characterization of a short-chain acyl dehydrogenase from Klebsiella pneumoniae and its application for high-level production of L-2, 3-butanediol. J Ind Microbiol Biotechnol 41:1425–1433CrossRefPubMedGoogle Scholar
  29. Rathnasingh C, Raj SM, Lee Y, Catherine C, Ashok S, Park S (2012) Production of 3-hydroxypropionic acid via malonyl-CoA pathway using recombinant Escherichia coli strains. J Biotechnol 157:633–640CrossRefPubMedGoogle Scholar
  30. Sabra W, Groeger C, Zeng AP (2015) Microbial cell factories for diol production. In: Bioreactor engineering research and industrial applications I. Springer, Berlin/Heidelberg, pp 165–197CrossRefGoogle Scholar
  31. Saddler JN, Ernest KC, Mes-Hartree M, Levitin N, Brownell HH (1983) Utilization of enzymatically hydrolyzed wood hemicelluloses by microorganisms for production of liquid fuels. Appl Environ Microbiol 45:153–160PubMedPubMedCentralGoogle Scholar
  32. Silveira MM, Berbert-Molina M, Prata AMR, Schmidell W (1998) Production of 2,3-butanediol from sucrose by Klebsiella pneumoniae NRRL B199 in batch and fed-batch reactors. Braz Arch Biol Techn 41:0–0CrossRefGoogle Scholar
  33. Song CW, Lee SY (2015) Combining rational metabolic engineering and flux optimization strategies for efficient production of fumaric acid. Appl Microbiol Biotechnol 99:8455–8464CrossRefPubMedGoogle Scholar
  34. Song CW, Kim DI, Choi S, Jang JW, Lee SY (2013) Metabolic engineering of Escherichia coli for the production of fumaric acid. Biotechnol Bioeng 110:2025–2034CrossRefPubMedGoogle Scholar
  35. Song CW, Kim JW, Cho IJ, Lee SY (2016) Metabolic engineering of Escherichia coli for the production of 3-hydroxypropionic acid and malonic acid through β-alanine route. ACS Synth Biol 5(11):1256–1263CrossRefPubMedGoogle Scholar
  36. Sun LH, Wang XD, Dai JY, Xiu ZL (2009) Microbial production of 2,3-butanediol from Jerusalem artichoke tubers by Klebsiella pneumoniae. Appl Microbiol Biotechnol 82:847–852CrossRefPubMedGoogle Scholar
  37. Syu MJ (2001) Biological production of 2, 3-butanediol. Appl Microbiol Biotechnol 55:10–18CrossRefPubMedGoogle Scholar
  38. Tsvetanova F, Petrova P, Petrov K (2014) 2,3-butanediol production from starch by engineered Klebsiella pneumoniae G31-a. Appl Microbiol Biotechnol 98:2441–2451CrossRefPubMedGoogle Scholar
  39. Valdehuesa KNG, Liu H, Nisola GM, Chung WJ, Lee SH, Park SJ (2013) Recent advances in the metabolic engineering of microorganisms for the production of 3-hydroxypropionic acid as C3 platform chemical. Appl Microbiol Biotechnol 97:3309–3321CrossRefPubMedGoogle Scholar
  40. Wang Y, Tashiro Y, Sonomoto K (2015) Fermentative production of lactic acid from renewable materials: recent achievements, prospects, and limits. J Biosci Bioeng 119:10–18CrossRefPubMedGoogle Scholar
  41. Xu Q, Li S, Huang H, Wen J (2012) Key technologies for the industrial production of fumaric acid by fermentation. Biotechnol Adv 30:1685–1696CrossRefPubMedGoogle Scholar
  42. Yamamoto H, Matsuyama A, Kobayashi Y (2002) Synthesis of (R)-1,3-butanediol by enantioselective oxidation using whole recombinant Escherichia coli cells expressing (S)-specific secondary alcohol dehydrogenase. Biosci Biotechnol Biochem 4:925–927CrossRefGoogle Scholar
  43. Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A, Boldt J, Khandurina J, Trawick JD, Osterhout RE, Stephen R, Estadilla J, Teisan S, Schreyer HB, Andrae S, Yang TH, Lee SY, Burk MJ, Dien SV (2011) Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat Chem Biol 7:445–452CrossRefPubMedGoogle Scholar
  44. Yu EKC, Levitin N, Saddler JN (1982) Production of 2, 3-butanediol by Klebsiella pneumoniae grown on acid hydrolyzed wood hemicellulose. Biotechnol Lett 4:741–746CrossRefGoogle Scholar
  45. Zhang X, Wang X, Shanmugam KT, Ingram LO (2011) L-malate production by metabolically engineered Escherichia coli. Appl Environ Microbiol 77:427–434CrossRefPubMedGoogle Scholar
  46. Zhang Y, Kumar A, Hardwidge PR, Tanaka T, Kondo A, Vadlani PV (2016) D-lactic acid production from renewable lignocellulosic biomass via genetically modified Lactobacillus plantarum. Biotechnol Pro 32(2):271–278CrossRefGoogle Scholar
  47. 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 69:399–407CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Division of Chemical Engineering and Materials ScienceEwha Womans UniversitySeoulKorea
  2. 2.Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea

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