Biotechnology Letters

, Volume 40, Issue 8, pp 1167–1179 | Cite as

Biosynthesis of d-lactic acid from lignocellulosic biomass

  • Yixing ZhangEmail author
  • Makoto Yoshida
  • Praveen V. Vadlani


d-lactic acid is a versatile and important industrial chemical that can be applied in the synthesis of thermal-resistant poly-lactic acid. Biosynthesis of d-lactic acid can be achieved by a variety of microorganisms, including lactic acid bacteria, yeast, and fungi; however, the final product yield, optical purity, and the utilization of both glucose and xylose are restricted. Consequently, engineered microbial systems are essential to attain high titer, productivity, and complete utilization of sugars. Herein, we critically evaluate the promising wild-type microorganisms, as well as genetically modified microorganisms to produce enantiomerically pure d-lactic acid, particularly from renewable lignocellulosic biomass. In addition, innovative bioreactor operation, metabolic flux analysis, and recent genetic engineering methods for targeted microbial d-lactic acid synthesis will be discussed.


d-lactic acid Lignocellulosic biomass Lactic acid bacteria Metabolic engineering 



This project was supported by the Consortium for Plant Biotechnology Research (CPBR), the Gary and Betty Lortscher Endowment, Department of Grain Science and Industry at Kansas State University, and Japan Society of Promotion of Science (17F17404).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abdel-Rahman MA, Tashiro Y, Sonomoto K (2011) Lactic acid production from lignocellulose-derived sugars using lactic acid bacteria: overview and limits. J Biotechnol 156:286–301CrossRefPubMedGoogle Scholar
  2. Abdel-Rahman MA, Tashiro Y, Sonomoto K (2013) Recent advances in lactic acid production by microbial fermentation processes. Biotechnol Adv 31:877–902CrossRefPubMedGoogle Scholar
  3. Baek SH, Kwon EY, Kim YH, Hahn JS (2016) Metabolic engineering and adaptive evolution for efficient production of D-lactic acid in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 100:2737–2748CrossRefPubMedGoogle Scholar
  4. Bai ZZ, Gao Z, Sun JF, Wu B, He BF (2016) D-lactic acid production by Sporolactobacillus inulinus YBS1-5 with simultaneous utilization of cottonseed meal and corncob residue. Bioresour Technol 207:346–352CrossRefPubMedGoogle Scholar
  5. Cui F, Li Y, Wan C (2011) Lactic acid production from corn stover using mixed cultures of Lactobacillus rhamnosus and Lactobacillus brevis. Bioresour Technol 102:1831–1836CrossRefPubMedGoogle Scholar
  6. Datta R, Tsai S, Bonsignore P, Moon S, Frank J (1995) Technological and economic-potential of poly(lactic Acid) and lactic-acid derivatives. FEMS Microbiol Rev 16:221–231CrossRefGoogle Scholar
  7. Dusselier M, Van Wouwe P, Dewaele A, Makshina E, Sels BF (2013) Lactic acid as a platform chemical in the biobased economy: the role of chemocatalysis. Energy Environ Sci 6:1415–1442CrossRefGoogle Scholar
  8. Eş I, Mousavi Khaneghah A, Barba FJ, Saraiva JA, Sant’Ana AS, Hashemi SMB (2018) Recent advancements in lactic acid production—a review. Food Res Int 107:763–770CrossRefPubMedGoogle Scholar
  9. Garlotta D (2001) A literature review of poly (lactic acid). J Polym Environ 9:63–84CrossRefGoogle Scholar
  10. Ghaffar T, Ghaffar M, Irshad Z, Anwar T, Aqil Z, Zulifqar A, Tariq M, Kamran N, Ehsan S, Mehmood S (2014) Recent trends in lactic acid biotechnology: a brief review on production to purification. J Radiat Res 7:222–229Google Scholar
  11. Hama S, Mizuno S, Kihara M, Tanaka T, Ogino C, Noda H, Kondo A (2015) Production of D-lactic acid from hardwood pulp by mechanical milling followed by simultaneous saccharificatoin and fermentation using metabolically engineered Lactobacillus plantarum. Bioresour Technol 187:167–172CrossRefPubMedGoogle Scholar
  12. Hofvendahl K, Hahn-Hagerdal B (2000) Factors affecting the fermentative lactic acid production from renewable resources. Enzyme Microb Technol 26:87–107CrossRefPubMedGoogle Scholar
  13. Jamshidian M, Tehrany EA, Imran M, Jacquot M, Desobry S (2010) Poly-lactic acid: production, applications, nanocomposites, and release studies. Compr Rev Food Sci Food Saf 9:552–571CrossRefGoogle Scholar
  14. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual—Rna-guided DNA endonuclease in adaptive bacterial immunity. Science 33:816–821CrossRefGoogle Scholar
  15. Joshi DS, Jain MS, Khire J, Gokhale D (2010) Strain improvement of Lactobaillus lactis for D-lactic acid production. Biotechnol Lett 32:517–520CrossRefPubMedGoogle Scholar
  16. Kandler O (1983) Carbohydrate metabolism in lactic acid bacteria. A Van Leeuw J Microb 49:209–224CrossRefGoogle Scholar
  17. Leja K, Myszka K, Czaczyk K (2011) Genome shuffling: a method to improve biotechnological processes. BioTechnologia 92:345–351CrossRefGoogle Scholar
  18. Liaud N, Rosso MN, Fabre N, Grapart S, Herpoël-Gimbert I, Sigoillot JC, Raouche S, Levasseur A (2015) L-lactic acid production by Aspergillus brasiliensis overexpressing the heterologous ldha gene from Rhizopus oryzae. Microb Cell Fact 14:66–75CrossRefPubMedPubMedCentralGoogle Scholar
  19. Liu Y, Liao W, Chen S (2008) Co-production of lactic acid and chitin using a pelletized filamentous fungus Rizopus oryzae cultured on cull potatoes and glucose. J Appl Microbiol 105:1521–1528CrossRefPubMedGoogle Scholar
  20. Lu HY, Zhao X, Wang YZ, Ding XR, Wang JH, Garza E, Manow R, Iverson A, Zhou SD (2016) Enhancement of D-lactic acid production from a mixed glucose and xylose substrate by the Escherichia coli strain JH15 devoid of the glucose effect. BMC Biol 16:19–29CrossRefGoogle Scholar
  21. Maas RHW, Bakker RR, Eggink G, Weusthuis RA (2006) Lactic acid production from xylose by the fungus Rhizopus oryzae. Appl Microbiol Biotechnol 72:861–868CrossRefPubMedGoogle Scholar
  22. Meussen BJ, de Graaff LH, Sanders JP, Weusthuis RA (2012) Metabolic engineering of Rhizopus oryzae for the production of platform chemicals. Appl Microbiol Biotechnol 94:875–886CrossRefPubMedPubMedCentralGoogle Scholar
  23. Mimitsuka T, Sawai K, Kobayashi K, Tsukada T, Tekeuchi N, Yamada K, Ogino H, Yonehara T (2015) Production of D-lactic acid in continuous membrane integrated fermentation reactor by genetically modified Saccharomyces cerevisiae: enhancement in d-lactic acid carbon yield. J Biosci Bioeng 119:65–71CrossRefPubMedGoogle Scholar
  24. Mussatto SI, Roberto IC (2004) Alternatives for detoxification of diluted-acid lignocellulosic hydrolyzates for use in fermentative processes: a review. Bioresour Technol 93:1–10CrossRefPubMedGoogle Scholar
  25. Nguyen CM, Kim JS, Song JK, Choi GJ, Choi YH, Jang KS, Kim JC (2012) D-lactic acid production from dry biomass of Hydrodictyon reticulatum by simultaneous saccharification and co-fermentation using Lactobacillus coryniformis subsp torquens. Biotechnol Lett 34:2235–2240CrossRefPubMedPubMedCentralGoogle Scholar
  26. Nguyen CM, Kim J, Nguyen Thanh Ngoc, Kim SK, Choi GJ, Choi YH, Jang KS, Kim J (2013) Production of L- and D-lactic acid from waste Curcuma longa biomass through simultaneous saccharification and cofermentation. Bioresour Technol 146:35–43CrossRefPubMedGoogle Scholar
  27. Ohara H, Owaki M, Sonomoto K (2007) Calculation of metabolic flow of xylose in Lactococcus lactis. BioSci Bioeng 1:92–94CrossRefGoogle Scholar
  28. Okano K, Kimura S, Narita J, Fukuda H, Kondo A (2007) Improvement in lactic acid production from starch using alpha-amylase-secreting Lactococcus lactis cells adapted to maltose or starch. Appl Microbiol Biotechnol 75:1007–1013CrossRefPubMedGoogle Scholar
  29. Okano K, Zhang Q, Shinkawa S, Yoshida S, Tanaka T, Fukuda H, Kondo A (2009a) Efficient production of optically pure D-lactic acid from raw corn starch by using a genetically modified L-lactate dehydrogenase gene-deficient and alpha-amylase-secreting Lactobacillus plantarum strain. Appl Environ Microbiol 75:462–467CrossRefPubMedGoogle Scholar
  30. Okano K, Yoshida S, Tanaka T, Ogino C, Fukuda H, Kondo A (2009b) Homo-D-Lactic acid fermentation from arabinose by redirection of the phosphoketolase pathway to the pentose phosphate Pathway in L-Lactate dehydrogenase gene-deficient Lactobacillus plantarum. Appl Environ Microbiol 75:5175–5178CrossRefPubMedPubMedCentralGoogle Scholar
  31. Okano K, Yoshida S, Yamada R, Tanaka T, Ogino Fukuda H, Kondo A (2009c) Improved production of homo-D-lactic acid via xylose fermentation by introduction of xylose assimilation genes and redirection of the phosphoketolase pathway to the pentose phosphate pathway in L-lactate dehydrogenase gene-deficient Lactobacillus plantarum. Appl Environ Microbiol 75:7858–7861CrossRefPubMedPubMedCentralGoogle Scholar
  32. Okano K, Zhang Q, Yoshida S, Tanaka T, Ogino C, Fukuda H, Kondo A (2010) D-lactic acid production from cellooligosaccharides and β-glucan using L-LDH gene-deficient and endoglucanase-secreting Lactobacillus plantarum. Appl Microbiol Biotechnol 85:643–650CrossRefPubMedGoogle Scholar
  33. Olofsson K, Bertilsson M, Lidé G (2008) A short review on SSF—an interesting process option for ethanol production from lignocellulosic feedstocks. Biotechnol Biofuels 1:7–21CrossRefPubMedPubMedCentralGoogle Scholar
  34. Pacheco A, Talaia G, Sá-Pessoa J, Bessa D, Gonçalves MJ, Moreira R, Queirós O (2012) Lactic acid production in Saccharomyces cerevisiae is modulated by expression of the monocarboxylate transporters Jen1 and Ady2. FEMS Yeast Res 12(3):375–381CrossRefPubMedGoogle Scholar
  35. Park EY, Kosakai Y, Okabe M (1998) Efficient production of L-lactic acid using mycelial cotton-like flocs of Rhizopus oryzae in an air-lift bioreactor. Biotechnol Progr 14:699–704CrossRefGoogle Scholar
  36. Park EY, Anh PN, Okuda N (2004) Bioconversion of waste office paper to L-lactic acid by the filamentous fungus Rhizopus oryzae. Bioresour Technol 93:77–83CrossRefPubMedGoogle Scholar
  37. Shi TQ, Liu GN, Ji RY, Shi K, Song P, Ren LJ, Huang H, Ji XJ (2017) CRISPR/Cas9-based genome editing of the filamentous fungi: the state of the art. Appl Microbiol Biotechnol 101:7435–7443CrossRefPubMedGoogle Scholar
  38. Singhvi M, Joshi D, Adsul M, Varma A, Gokhale D (2010) D-lactic acid production from cellobiose and cellulose by Lactobacillus lactis mutant RM2-24. Green Chem 12:1106–1109CrossRefGoogle Scholar
  39. Taniguchi M, Tokunaga T, Horiuchi K, Hoshino K, Sakai K, Tanaka T (2004) Production of L-lactic acid from a mixture of xylose and glucose by co-cultivation of lactic acid bacteria. Appl Microbiol Biotechnol 66:160–165CrossRefPubMedGoogle Scholar
  40. Taskila S, Ojamo H (2013) The current status and future expectations in industrial production of lactic acid by lactic acid bacteria. In: Kongo M (ed) Lactic acid bacteria: R&D for food, health and livestock purposes. Accessed 24 Jan 2018
  41. 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 80:1–12CrossRefPubMedGoogle Scholar
  42. Tokuhiro K, Ishida N, Nagamori E, Saitoh S, Onishi T, Kondo A, Takahashi H (2009) Double mutation of the PDC1 and ADH1 genes improves lactate production in the yeast Saccharomyces cerevisiae expressing the bovine lactate dehydrogenase gene. Appl Microbiol Biotechnol 82:883–890CrossRefPubMedGoogle Scholar
  43. Tsuji H, Ikada Y (1999) Physical properties of polylactides. Curr Trends Polym Sci 4:27Google Scholar
  44. Vijayakumar J, Aravindan R, Viruthagiri T (2008) Recent trends in the production, purification and application of lactic acid. Chem Biochem Eng Q 22:245–264Google Scholar
  45. Wang L, Zhao B, Liu B, Yu B, Ma C, Su F, Hua D, Li Q, Ma Y, Xu P (2010) Efficient production of L-lactic acid from corncob molasses, a waste by-product in xylitol production, by a newly isolated xylose utilizing Bacillus sp. strain. Bioresour Technol 101:7908–7915CrossRefPubMedGoogle Scholar
  46. Xu TT, Bai ZZ, Wang LJ, He BF (2010) Breeding of D-lactic acid high producing strain by low-energy ion implantation and preliminary analysis of related metabolism. Appl Biochem Biotechnol 160:312–321Google Scholar
  47. Yadav AK, Chaudhari AB, Kothari RM (2011) Bioconversion of renewable resources into lactic acid: an industrial view. Crit Rev Biotechnol 31:1–19CrossRefPubMedGoogle Scholar
  48. Zaunmueller T, Eichert M, Richter H, Unden G (2006) Variations in the energy metabolism of biotechnologically relevant heterofermentative lactic acid bacteria during growth on sugars and organic acids. Appl Microbiol Biotechnol 72:421–429CrossRefGoogle Scholar
  49. Zhang Y, Vadlani PV (2013) D-lactic acid biosynthesis from biomass-derived sugars via Lactobacillus delbrueckii fermentation. Bioproc Biosyst Eng 36:1897–1904CrossRefGoogle Scholar
  50. Zhang YX, Vadlani PV (2015) Lactic acid production from biomass-derived sugars via co-fermentation of Lactobacillus brevis and Lactobacillus plantarum. J Biosci Bioeng 119:694–699CrossRefPubMedGoogle Scholar
  51. Zhang YX, Kumar A, Hardwidge PR, Tanaka T, Kondo A, Vadlani PV (2016a) D-lactic acid production from renewable lignocellulosic biomass via genetically modified Lactobacillus plantarum. Biotechnol Prog 32:271–278CrossRefPubMedGoogle Scholar
  52. Zhang YX, Vadlani PV, Kumar A, Hardwidge PR, Govind R, Tanaka T, Kondo A (2016b) Enhanced D-lactic acid production from renewable resources using engineered Lactobacillus plantarum. Appl Microbiol Biotechnol 100:279–288CrossRefPubMedGoogle Scholar
  53. Zhang YX, Zeng F, Hohn K, Vadlani PV (2016c) Metabolic flux analysis of carbon balance in Lactobacillus strain. Biotehcnol Prog 32:1397–1403CrossRefGoogle Scholar
  54. Zhao JF, Xu LY, Wang YZ, Zhao X, Wang JH, Garza E, Manow R, Zhou SD (2013) Homofermentative production of optically pure L-lactic acid from xylose by genetically engineered Escherichia coli B. Microb Cell Fact 12:57–63CrossRefPubMedPubMedCentralGoogle Scholar
  55. Zhao T, Liu D, Ren H, Shi X, Zhao N, Chen Y, Ying H (2014) D-Lactic acid production by Sporolactobacillus inulinus Y2-8 immobilized in fibrous bed bioreactor using corn flour hydrolyzate. J Microbiol Biotechnol 24:1664–1672CrossRefPubMedGoogle Scholar
  56. Zheng HJ, Gong JX, Chen T, Chen X, Zhao XM (2010) Strain improvement of Sporolactobacillus inulinus ATCC 15538 for acid tolerance and production of D-lactic acid by genome shuffling. Appl Microbiol Biotechnol 85:1541–1549CrossRefPubMedGoogle Scholar
  57. Zhou SD, Causey TB, Hasona A, Shanmugam KT, Ingram LO (2003) Production of optically pure D-lactic acid in mineral medium by metabolically engineered Escherichia coli W3110. Appl Environ Microbiol 69:399–407CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Bioprocessing and Renewable Energy Laboratory, Department of Grain Science & IndustryKansas State UniversityManhattanUSA
  2. 2.Department of Environmental and Natural Resource ScienceTokyo University of Agriculture and TechnologyTokyoJapan
  3. 3.Saivera BioPuttaparthiIndia
  4. 4.Department of Environmental and Natural Resource ScienceTokyo University of Agriculture and TechnologyTokyoJapan

Personalised recommendations