Skip to main content
Log in

Optimization and kinetic modeling of media composition for hyaluronic acid production from carob extract with Streptococcus zooepidemicus

  • Research Paper
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

Hyaluronic acid (HA), a mucopolysaccharide belonging to the glycosaminoglycan family, consists of repeating disaccharide units and has been used directly or indirectly in numerous human health practices. This study focused on evaluating carob pods for microbial HA production and kinetic modeling of HA fermentation. Therefore, the optimal medium composition was determined using Plackett–Burman Design (PBD) for HA production from carob extract with Streptococcus zooepidemicus. Maximum HA production of shake flask fermentation was 2.6 g/L (1.25 × 106) in the optimum medium, comprising 10°Bx of carob pods extract, 0.5 g/L of MgSO4.7H2O, 10.0 g/L of casein, 2.5 g/L of KH2PO4, 2.0 g/L of NaCl, 1.5 g/L of K2HPO4, 0.002 g/L of FeSO4 and 10.0 g/L of beef extract. In the continuation of the study, the fermentation performed with the optimal medium composition was modeled using three different models including the logistic model for biomass production, the Luedeking–Piret model for HA production, and the modified Luedeking–Piret model for substrate consumption. Based on the results, the experimental HA production data agreed with the Luedeking–Piret model with an R2 of 0.989. Since the α value was 63-fold higher than the value of β, the HA production is growth-associated. Consequently, carob extract can be evaluated as a promising carbon source for producing HA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Meyer K, Palmer JW (1934) The polysaccharide of the vitreous humor. J Biol Chem 107(3):629–634

    Article  CAS  Google Scholar 

  2. Fallacara A, Baldini E, Manfredini S, Vertuani S (2018) Hyaluronic acid in the 3rd millennium. Polymers. https://doi.org/10.3390/polym10070701

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sze JH, Brownlie JC, Love CA (2016) Biotechnological production of hyaluronic acid: a mini review. 3 Biotech 6(1):67

    Article  PubMed  PubMed Central  Google Scholar 

  4. Salwowska NM, Bebenek KA, Żądło DA, Wcisło-Dziadecka DL (2016) Physiochemical properties and application of hyaluronic acid: a systematic review. J Cosmet Dermatol 15(4):520–526

    Article  PubMed  Google Scholar 

  5. Volpi N, Schiller J, Stern R, Soltes L (2009) Role, metabolism, chemical modifications and applications of hyaluronan. Curr Med Chem 16(14):1718–1745

    Article  CAS  PubMed  Google Scholar 

  6. Kogan G, Šoltés L, Stern R, Gemeiner P (2007) Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotech Lett 29(1):17–25

    Article  CAS  Google Scholar 

  7. DeRosa TF (2012) Next generation of international chemical additives: a critical review of current US patents. Elsevier, New York

    Google Scholar 

  8. Qassemyar Q, Gianfermi M (2015) Supermicrosurgery and hyaluronic acid: experimental feasability study of a new method. In: Annales de Chirurgie Plastique Esthétique, vol 1. Elsevier, New York, pp 59–65

    Google Scholar 

  9. Vasi A-M, Popa MI, Butnaru M, Dodi G, Verestiuc L (2014) Chemical functionalization of hyaluronic acid for drug delivery applications. Mater Sci Eng, C 38:177–185

    Article  CAS  Google Scholar 

  10. Yatmaz E, Turhan İ (2015) Hyaluronik asit ve fermantasyonla üretilmesi. Gıda 40(4):233–240

    Google Scholar 

  11. GVR (2021) Grand View Research: Hyaluronic Acid Market Size Worth $16.6 Billion By 2027|CAGR: 8.1%. https://www.grandviewresearch.com/press-release/global-hyaluronic-acid-market, (Accessed 31/10/2021).

  12. Yamada T, Kawasaki T (2005) Microbial synthesis of hyaluronan and chitin: New approaches. J Biosci Bioeng 99(6):521–528

    Article  CAS  PubMed  Google Scholar 

  13. Boeriu CG, Springer J, Kooy FK, van den Broek LA, Eggink G (2013) Production methods for hyaluronan. Int J Carbohydr Chem. https://doi.org/10.1155/2013/624967

    Article  Google Scholar 

  14. de Oliveira JD, Carvalho LS, Gomes AMV, Queiroz LR, Magalhães BS, Parachin NS (2016) Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms. Microb Cell Fact 15(1):1–19

    Article  Google Scholar 

  15. Vázquez JA, Montemayor MI, Fraguas J, Murado MA (2010) Hyaluronic acid production by Streptococcus zooepidemicus in marine by-products media from mussel processing wastewaters and tuna peptone viscera. Microb Cell Fact 9(1):1–10

    Article  Google Scholar 

  16. Amado IR, Vázquez JA, Pastrana L, Teixeira JA (2017) Microbial production of hyaluronic acid from agro-industrial by-products: molasses and corn steep liquor. Biochem Eng J 117:181–187

    Article  CAS  Google Scholar 

  17. Pan NC, Pereira HCB, da Silva MdLC, Vasconcelos AFD, Celligoi MAPC (2017) Improvement production of hyaluronic acid by Streptococcus zooepidemicus in sugarcane molasses. Appl Biochem Biotech 182(1):276–293

    Article  CAS  Google Scholar 

  18. Pires AM, Macedo AC, Eguchi SY, Santana MH (2010) Microbial production of hyaluronic acid from agricultural resource derivatives. Biores Technol 101(16):6506–6509

    Article  CAS  Google Scholar 

  19. Rohit SG, Jyoti PK, Subbi RRT, Naresh M, Senthilkumar S (2018) Kinetic modeling of hyaluronic acid production in palmyra palm (Borassus flabellifer) based medium by Streptococcus zooepidemicus MTCC 3523. Biochem Eng J 137:284–293

    Article  CAS  Google Scholar 

  20. Ayaz FA, Torun H, Ayaz S, Correia PJ, Alaiz M, Sanz C, Gruz J, Strnad M (2007) Determination of chemical composition of anatolian carob pod (Ceratonia siliqua L.): sugars, amino and organic acids, minerals and phenolic compounds. J Food Qual 30(6):1040–1055

    Article  CAS  Google Scholar 

  21. Biner B, Gubbuk H, Karhan M, Aksu M, Pekmezci M (2007) Sugar profiles of the pods of cultivated and wild types of carob bean (Ceratonia siliqua L.) in Turkey. Food Chem 100(4):1453–1455

    Article  CAS  Google Scholar 

  22. Ercan Y, Irfan T, Mustafa K (2013) Optimization of ethanol production from carob pod extract using immobilized Saccharomyces cerevisiae cells in a stirred tank bioreactor. Biores Technol 135:365–371

    Article  CAS  Google Scholar 

  23. Germec M, Karhan M, Demirci A, Turhan I (2018) Ethanol production in a biofilm reactor with non-sterile carob extract media and its modeling. Energy Sour Part A Recover Util Environ Eff 40(22):2726–2734

    Article  CAS  Google Scholar 

  24. Germec M, Turhan I, Demirci A, Karhan M (2016) Effect of media sterilization and enrichment on ethanol production from carob extract in a biofilm reactor. Energy Sour Part A Recov Util Environ Eff 38(21):3268–3272

    Article  CAS  Google Scholar 

  25. Germec M, Turhan I, Karhan M, Demirci A (2015) Ethanol production via repeated-batch fermentation from carob pod extract by using Saccharomyces cerevisiae in biofilm reactor. Fuel 161:304–311

    Article  CAS  Google Scholar 

  26. Turhan I, Bialka KL, Demirci A, Karhan M (2010) Ethanol production from carob extract by using Saccharomyces cerevisiae. Biores Technol 101(14):5290–5296

    Article  CAS  Google Scholar 

  27. Haider MM (2014) Citric acid production from carob pod extract by Aspergillus niger. J Pharm Biol Sci 9:112–116

    Google Scholar 

  28. Turhan I, Bialka KL, Demirci A, Karhan M (2010) Enhanced lactic acid production from carob extract by Lactobacillus casei using invertase pretreatment. Food Biotechnol 24(4):364–374

    Article  CAS  Google Scholar 

  29. Germec M, Yatmaz E, Karahalil E, Turhan I (2017) Effect of different fermentation strategies on β-mannanase production in fed-batch bioreactor system. 3 Biotech 7:77

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gürler HN, Erkan SB, Ozcan A, Yılmazer C, Karahalil E, Germec M, Yatmaz E, Ogel ZB, Turhan I (2021) Scale-up processing with different microparticle agent for β-mannanase production in a large-scale stirred tank bioreactor. J Food Process Preserv 45(8):e14915

    Article  Google Scholar 

  31. Karahalil E, Germec M, Karaoglan M, Yatmaz E, Coban HB, Inan M, Turhan I (2020) Partial purification and characterization of a recombinant β-mannanase from Aspergillus fumigatus expressed in Aspergillus sojae grown on carob extract. Biomass Conv Bioref 10:1189–1205

    Article  CAS  Google Scholar 

  32. Karahalil E, Germec M, Turhan I (2019) β-mannanase production and kinetic modeling from carob extract by using recombinant Aspergillus sojae. Biotechnol Prog 35(6):e2885. https://doi.org/10.1002/btpr.2885

    Article  CAS  PubMed  Google Scholar 

  33. Yatmaz E, Karahalil E, Germec M, Ilgin M, Turhan I (2016) Controlling filamentous fungi morphology with microparticles to enhanced β-mannanase production. Bioprocess Biosyst Eng 39(9):1391–1399

    Article  CAS  PubMed  Google Scholar 

  34. Yatmaz E, Karahalil E, Germec M, Oziyci HR, Karhan M, Ogel ZB, Duruksu G, Turhan I (2016) Enhanced β-mannanase production from alternative sources by recombinant Aspergillus sojae. Acta Aliment 45(3):371–379

    Article  CAS  Google Scholar 

  35. Yilmazer C, Gürler HN, Erkan SB, Ozcan A, Hosta Yavuz G, Germec M, Yatmaz E, Turhan I (2021) Optimization of mannooligosaccharides production from different hydrocolloids via response surface methodology using a recombinant Aspergillus sojae β-mannanase produced in the microparticle-enhanced large-scale stirred tank bioreactor. J Food Process Preserv 45(8):e14916

    Article  CAS  Google Scholar 

  36. Germec M, Turhan I (2019) Evaluation of carbon sources for the production of inulinase by Aspergillus niger A42 and its characterization. Bioprocess Biosyst Eng 42:1993–2005

    Article  CAS  PubMed  Google Scholar 

  37. Ilgın M, Germec M, Turhan I (2020) Inulinase production and mathematical modeling from carob extract by using Aspergillus niger. Biotechnol Prog. https://doi.org/10.1002/btpr.2919

    Article  PubMed  Google Scholar 

  38. Ilgın M, Germec M, Turhan I (2020) Statistical and kinetic modeling of Aspergillus niger inulinase fermentation from carob extract and its partial concentration. Ind Crops Prod 156:112866

    Article  Google Scholar 

  39. Smail T, Salhi O, Knapp J (1995) Solid-state fermentation of carob pods by Aspergillus niger for protein production: effect of particle size. World J Microbiol Biotechnol 11(2):171–173

    Article  CAS  PubMed  Google Scholar 

  40. Yatmaz E, Turhan I (2018) Carob as a carbon source for fermentation technology. Biocatal Agric Biotechnol 16:200–208

    Article  Google Scholar 

  41. Germec M, Turhan I, Karhan M, Demirci A (2019) Kinetic modeling and techno-economic feasibility of ethanol production from carob extract based medium in biofilm reactor. Appl Sci 9(10):2121

    Article  CAS  Google Scholar 

  42. Germec M, Turhan I (2021) Kinetic modeling and sensitivity analysis of inulinase production in large-scale stirred tank bioreactor with sugar beet molasses-based medium. Biochem Eng J 176:108201

    Article  CAS  Google Scholar 

  43. Shinto H, Tashiro Y, Yamashita M, Kobayashi G, Sekiguchi T, Hanai T, Kuriya Y, Okamoto M, Sonomoto K (2007) Kinetic modeling and sensitivity analysis of acetone–butanol–ethanol production. J Biotechnol 131(1):45–56

    Article  CAS  PubMed  Google Scholar 

  44. Don MM, Shoparwe NF (2010) Kinetics of hyaluronic acid production by Streptococcus zooepidemicus considering the effect of glucose. Biochem Eng J 49(1):95–103

    Article  CAS  Google Scholar 

  45. Huang W-C, Chen S-J, Chen T-L (2007) Modeling the microbial production of hyaluronic acid. J Chin Inst Chem Eng, 38(3–4):355–359

    Article  CAS  Google Scholar 

  46. Bitter T (1962) A modified uronic acid carbazole reaction. Anal Biochem 4:330–334

    Article  CAS  PubMed  Google Scholar 

  47. Amado IR, Vázquez JA, Pastrana L, Teixeira JA (2016) Cheese whey: A cost-effective alternative for hyaluronic acid production by Streptococcus zooepidemicus. Food Chem 198:54–61

    Article  CAS  PubMed  Google Scholar 

  48. Miller GL (1959) Use of dinitrosalicylic acid reagent for determination of reducing sugar. Anal Chem 31(3):426–428

    Article  CAS  Google Scholar 

  49. Germec M, Gürler HN, Ozcan A, Erkan SB, Karahalil E, Turhan I (2020) Medium optimization and kinetic modeling for the production of Aspergillus niger inulinase. Bioprocess Biosyst Eng 43(2):217–232. https://doi.org/10.1007/s00449-019-02219-1

    Article  CAS  PubMed  Google Scholar 

  50. Germec M, Turhan I (2021) Predicting the experimental data of the substrate specificity of Aspergillus niger inulinase using mathematical models, estimating kinetic constants in the Michaelis-Menten equation, and sensitivity analysis. Biomass Conv Bioref. https://doi.org/10.1007/s13399-021-01830-1

    Article  Google Scholar 

  51. Cheng K-C, Demirci A, Catchmark JM, Puri VM (2010) Modeling of pullulan fermentation by using a color variant strain of Aureobasidium pullulans. J Food Eng 98(3):353–359

    Article  CAS  Google Scholar 

  52. Chai T, Draxler R (2014) Root mean square error (RMSE) or mean absolute error (MAE)?–Arguments against avoiding RMSE in the literature. Geoscientific Model Dev 7(3):1247–1250

    Article  Google Scholar 

  53. Erkan SB, Yatmaz E, Germec M, Turhan I (2021) Effect of furfural concentration on ethanol production using Saccharomyces cerevisiae in an immobilized cells stirred-tank bioreactor with glucose-based medium and mathematical modeling. J Food Process Preserv 45(8):e14635

    Article  CAS  Google Scholar 

  54. Germec M, Cheng K-C, Karhan M, Demirci A, Turhan I (2020) Application of mathematical models to ethanol fermentation in biofilm reactor with carob extract. Biomass Conv Bioref 10(2):237–252

    Article  CAS  Google Scholar 

  55. Germec M, Ozcan A, Turhan I (2019) Bioconversion of wheat bran into high value-added products and modelling of fermentations. Ind Crops Prod 139:111565

    Article  CAS  Google Scholar 

  56. Germec M, Turhan I (2018) Ethanol production from acid-pretreated and detoxified rice straw as sole renewable resource. Biomass Conv Bioref 8(3):607–619

    Article  CAS  Google Scholar 

  57. Patil KP, Patil DK, Chaudhari BL, Chincholkar SB (2011) Production of hyaluronic acid from Streptococcus zooepidemicus MTCC 3523 and its wound healing activity. J Biosci Bioeng 111(3):286–288

    Article  CAS  PubMed  Google Scholar 

  58. Armstrong D, Cooney M, Johns M (1997) Growth and amino acid requirements of hyaluronic-acid-producing Streptococcus zooepidemicus. Appl Microbiol Biotechnol 47(3):309–312

    Article  CAS  Google Scholar 

  59. Mohan N, Balakrishnan R, Sivaprakasam S (2016) Optimization and effect of dairy industrial waste as media components in the production of hyaluronic acid by Streptococcus thermophilus. Prep Biochem Biotechnol 46(6):628–638

    Article  CAS  PubMed  Google Scholar 

  60. Zeng AP, Ross A, Biebl H, Tag C, Günzel B, Deckwer WD (1994) Multiple product inhibition and growth modeling of Clostridium butyricum and Klebsiella pneumoniae in glycerol fermentation. Biotechnol Bioeng 44(8):902–911

    Article  CAS  PubMed  Google Scholar 

  61. Shuler M, Kargi F, DeLisa M (2017) Bioprocess engineering: basic concepts, 3rd edn. Prentice Hall, Upper Saddle River

    Google Scholar 

  62. Germec M, Turhan I (2021) Application of Aspergillus niger inulinase production in sugar beet molasses-based medium optimized by Central Composite Design to mathematical models. Biomass Conv Bioref. https://doi.org/10.1007/s13399-021-01923-x

    Article  Google Scholar 

  63. Im J-H, Song J-M, Kang J-H, Kang D-J (2009) Optimization of medium components for high-molecular-weight hyaluronic acid production by Streptococcus sp. ID9102 via a statistical approach. J Ind Microbiol Biotechnol 36(11):1337

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author was supported by the Scientific and Research Council of Turkey (TUBITAK) Domestic Priority Areas Post-Graduate Scholarship Program (2210-C). This research was supported by the Akdeniz University Research Foundation (Project Number: FYL-2019-4723).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Irfan Turhan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest in the publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ozcan, A., Germec, M. & Turhan, I. Optimization and kinetic modeling of media composition for hyaluronic acid production from carob extract with Streptococcus zooepidemicus. Bioprocess Biosyst Eng 45, 2019–2029 (2022). https://doi.org/10.1007/s00449-022-02806-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-022-02806-9

Keywords

Navigation