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Hyaluronic acid production

Optimization of extraction and production methods of Hyaluronic Acid (HA) from Streptococcus zooepidemicus

Surajit Baksi, Mukandar Khan, Mamta Panchal, Nirav Rao


Hyaluronic acid (HA) is a biopolysacharride present in connective tissues of body. It has high significant economic concern due to its high use in medical, cosmetic and food industries. It is present in several resources like rooster combs, eye and umbilical cord. Due to its good chemical and physical properties, it is used in ophthalmic and osteoarthritic surgeries. Presently, it is produced from animal and bacterial sources. But, the percentage yield is very less at large scale. In present study, effort was done to increase yield of HA from Streptococcus zooepidemicus, through modification of the fermentation and extraction process. The cell concentration and HA concentration was measured which showed that HA concentration increased with induced pH stress.


Hyaluronic acid; Production; Bacteria; Extraction

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K. Meyer, J.W. Palmer. The polysaccharide of the vitreous humor. J. Biol. Chem.1934, 107, 629–634.

B. F. Chong, L. M. Blank, R. Mclaughlin, L. K. Nielsen. Microbial hyaluronic acid production. Appl. Microbiol. Biotechnol. 2005, 66, 341–351.

D.D. Allison, K.J. Grande-Allen. Review. Hyaluronan: a powerful tissue engineering tool. Tissue. Eng. 2006, 12, 2131–2140.

S. Fagien, D. Cassuto. Reconstituted injectable hyaluronic acid: expanded applications in facial aesthetics and additional thoughts on the mechanism of action in cosmetic medicine. Plast. Reconstr. Surg. 2012, 130, 208–217.

G. Kogan, L. Soltes, R. Stern, P. Gemeiner. Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol. Lett. 2007, 29, 17–25.

C.A. Cooper, K.K. Brown, C.D. Meletis, N. Zabriskie. Inflammation and hyaluronic acid. Altern. Complement. Ther. 2008, 14, 78–84.

R. Stern, A.A. Asari, K.N. Sugahara. Hyaluronan fragments: an information-rich system. Eur. J. Cell. Biol. 2006, 85, 699–715.

J. Singh and B. Chhikara. Comparative global epidemiology of HIV infections and status of current progress in treatment. Chem. Biol. Lett. 2014, 1,1, 14-32.

B. Chhikara. Prospects of Applied Nanomedicine. Appl. Nanomed. 2016,1(1), 1-2.

R. Upadhyay and A. Khed. A comparative study of inhibitive effects of some Schiff’s Bases on Mild Steel in Acid media. J. Integr. Sci. Technol. 2016, 4(2), 90-95.

J. Nipa, M. Amin, M. Rahman, F. Sharmin, P. Karmakar, M. Choudhuri. Investigation of hematologic parameter of an Ayurvedic preparation “Amalaki Rasayan†used in jaundice after chronic administration to sprague-dawley rats. J. Biomed. Ther. Sci. 2016, 3(1), 1-6.

S. Sharma. Unprecedented Palladium catalyzed Homo-Coupling Reaction of terminal E-diiodoalkanes towards the synthesis of Buta-1,3-diynes. Adv. Org. Chem. Lett. 2017, 4(1), 1-3.

L. Jr. Lapcík, L. Lapcík, S. De Smedt, J. Demeester, P. ChabreÄek, Hyaluronan: Preparation, structure, properties, and applications. Chem. Rev. 1998, 98, 2663–2684.

B. Fong Chong and L. K. Nielsen. Amplifying the cellular reduction potential of Streptococcus zooepidemicus. J. Biotechnol. 2003a, 100, 33–41.

B. Fong Chong and L. K. Nielsen. Aerobic cultivation of Streptococcus zooepidemicus and the role of NADH oxidase. Biochem. Eng. J. 2003b, 16, 153–162.

L.M. Blank, P. Hugenholtz, L.K. Nielsen. Evolution of the hyaluronic acid synthesis (has) operon in Streptococcus zooepidemicus and other pathogenic Streptococci. J. Mol. Evo. 2008, 67, 13–22.

P.L. Deangelis. Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow. Appl. Microbiol. Biotechnol. 2012, 94, 295–305.

Jong, C.H. Wu, H.M. Chen, F. Luo, K.J. Kwon-Chung, Y.C. Chang, C.W. Lamunyon, A. Plaas, S. H. Huang. Identification and characterization of CPS1 as a hyaluronic acid synthase contributing to the pathogenesis of Cryptococcus neoformans infection. E C 2007, 6, 1486–1496.

J.H. Sze, C. Jeremy, C. Brownlie, A. Christopher, A. Love. Biotechnological production of hyaluronic acid: a mini review. Biotech. 2016, 6, 67.

C. Schiraldi, L.G. Annalisa and D.R. Mario. Biotechnological Production and Application of Hyaluronan, Biopolymers, Magdy Elnashar (Ed.), ISBN: 978-953-307-109-1, InTech, Available from: applicationof-hyaluronan 2010.

K.K. Brown, L.L. Ruiz, I. Van de Rijn, N.D. Greene, S.L. Trump, C.D. Wilson, S.A. Bryant. Method for the microbiological production of non-antigenic hyaluronic acid. US Patent 5316926. 1994, (

H.Y. Han, S.H. Jang, E.C. Kim, J.K. Park, Y.J. Han, C. Lee, H.S. Park, Y.C. Kim, H.J. Park. Microorganism producing hyaluronic acid and purification method of hyaluronic acid. Patent: WO 2004/016771. 2004.

S. Carlino and F. Magnette. Process for purifying high molecular weight hyaluronic acid. US Patent 6489467. 2002, (

J. Reddy and J. Karunakaran. Purification and characterization of hyaluronic acid produced by Streptococcus zooepidemicus strain 3523-7. BioSci. Biotech. 2013, 2(3), 173-179.

T. Bitter and H.M. Muir. A modified uronic acid carbazole reaction. Anal. Biochem.1962, 4(4), 330¬-334.

V. Rijn and R.E. Kessler. Growth characteristics of group A streptococci in a new chemically defined medium. Infect. Immun. 1980, 27, 444-448.

L. Liu, M. Wang, G. Du, J. Chen. Enhanced hyaluronic acid production of Streptococcus zooepidemicus by an intermittent alkaline-stress strategy. Letters. in Appl. Microbiol. 2008, 46, 383–388.

M.R. Johns, L.T. Goh, A. Oeggerli. Effect of pH, agitation and aeration on hyaluronic acid production byStreptococcus zooepidemicus. Biotech. Lett. 1994,16,5,507-512.

V. Rangaswamy and D. Jain. An efficient process for production and purification of hyaluronic acid from Streptococcus equi subsp. zooepidemicus. Biotechnol. Lett.2008,30(3),493-6.

S.J. Kim, S.Y. Park., C.W. Kim. A Novel approach to the production of hyaluronic acid by Streptococcus zooepidemicus. J. Microbial. and Biotech. 2006, 16(12), 1849-1855.


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