Hyaluronic acid production for therapeutic and cosmetic use by biotechnological process using recombinant Kluyveromyces lactis yeast

• Grant number: 21/11988-3
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Duration: March 01, 2022 - April 30, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Convênio/Acordo: SEBRAE-SP
• Principal Investigator: Antonio Milton Vieira Gomes
• Grantee: Antonio Milton Vieira Gomes
• Host Company: Biobreyer Pesquisa e Desenvolvimento Científico Ltda
• CNAE: Comércio atacadista de instrumentos e materiais para uso médico, cirúrgico, ortopédico e odontológico ; Pesquisa e desenvolvimento experimental em ciências físicas e naturais ; Atividades profissionais, científicas e técnicas não especificadas anteriormente
• City: Santos
• Pesquisadores principais:( Últimos ): Otto Werner Heringer
• Pesquisadores principais:( Antigos ): Raquel Tayar Nogueira
• Associated researchers: Renata Bannitz Fernandes
• Associated grant(s): 21/14956-5 - Hyaluronic acid production for therapeutic and cosmetic use by biotechnological process using recombinant Kluyveromyces lactis yeast, AP.PIPE
• Associated scholarship(s): 22/07389-0 - Hyaluronic acid production for therapeutic and cosmetic use by biotechnological process using recombinant Kluyveromyces lactis yeast, BP.TT; 22/04275-3 - Production of hyaluronic acid for therapeutic and cosmetic use by biotechnological process using recombinant Kluyveromyces lactis yeast, BP.PIPE

Abstract

The Hyaluronic Acid (HA) is a biopolymer composed of alternating repetitions of glucuronic acid (GlcUA) and N-acetyl glucosamine (GlcNAc) and is present in all vertebrates. According to projections performed by the company "Grand View Research", the global HA market was valued at 10.80 billion dollars in 2020 and is projected to be a compound annual growth of 8.1%, in addition to reaching the market value of 14.48 billion USD in 2027. Due to its rheological and physicochemical properties, HA is used in the formulation of various cosmetics, products associated with medical surgery, food supplementation, as well in the areas of medicines, ophthalmology, orthopedics, rheumatology, and dermatology. In Brazil, the HA used in products is mostly imported from other countries. HA is naturally produced by bacteria from the Streptococcus genus, which are pathogenic and consequently difficult for microorganism manipulation in the laboratory and subsequent cultivation in bioreactors. The scale-up process of technologies using these cells is also delayed due to biosafety and purification costs. As an alternative to these bacteria, genetically modified organisms (GMOs) have been developed to synthesize HA, reaching production values similar to those of bacteria of the genus Streptococcus. In Brazil, a GMO strain of the yeast Kluyveromyces lactis, called BAP strain, was previously modified to produce HA. This was the first study in the literature to use K. lactis as a platform for HA synthesis; the first HA GMO producing yeast created in Brazil and the second in the world. Bioreactor cultures using the BAP strain showed productivity of 1.89 g/L of HA without any optimization of culture medium and fermentation condition. In this context, the objective of this work is the development of an economically viable and scalable process for the production of cosmetic and medical grade HA using K. lactis. Optimization of culture media and certain production conditions will be performed in a bioreactor. Purification techniques will also be optimized in order to obtain HA of a purity grade compatible with cosmetic and medical applications. During all these stages of development, technical and economic evaluations of the process will be performed in order to reduce cost and improve process efficiency. Finally, deep characterization of the HA produced by K. lactis will be performed following quality standards established by pharmacopeias and regulatory agencies, and safety tests will also be carried out in cell and tissue cultures. Concomitant to the R&D process, the commercial development of the project will be carried out. Initially, the objective is the commercialization of HA produced by K. lactis as a research product (Research Use Only). Later, with the advancement of the process development, it is intended to obtain quality certifications to reach the cosmetic market, such as companies that use HA in the formulations of creams, shampoos, and sunscreens. Finally, the long-term commercial objective is the production of HA aimed at big markets, such as ophthalmology, orthopedics, rheumatology, and dermatology. In Brazil, there is currently no technology for the production of HA by GMOs, and only a few studies are focused on the characterization of HA produced by pathogenic strains. After the end of this project, it is expected the creation of the first Brazilian GMO strain that produces HA with the potential to compete with other strains existing in the world. Furthermore, the creation of the first national technology used for the production of HA in Brazil is expected. (AU)