Scaling Up the Production Process of Hyaluronic Acid Produced by Recombinant Kluyveromyces lactis

• Grant number: 24/09294-1
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Carlos Alexandre Breyer
• Grantee: Carlos Alexandre Breyer
• Company: Biobreyer Pesquisa e Desenvolvimento Científico Ltda
• CNAE: Testes e análises técnicas ; Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: Santos
• Associated research grant: 21/11988-3 - Hyaluronic acid production for therapeutic and cosmetic use by biotechnological process using recombinant Kluyveromyces lactis yeast, AP.PIPE

Abstract

Hyaluronic Acid (HA) is a biopolymer widely used in the cosmetic, healthcare, and dietary supplement industries due to its moisturizing and regenerative properties. This project aims to scale up the production of HA using genetically modified Kluyveromyces lactis yeast, aiming to reduce dependency on imports and meet the growing demand with a high-quality and sustainable product. During the PIPE Phase 2 (Process 2021/11988-3), laboratory-scale processes were established, including a pilot production test in a 100 L bioreactor. The present PIPE INVEST project aims to scale up the production process to larger volumes (100 and 1000 L) with an emphasis on downstream stages such as microfiltration, ultrafiltration, chromatography, and drying. The specific objectives include: 1) conducting fermentations in 100 L bioreactors, validating process reproducibility and optimizing critical parameters; 2) optimizing the microfiltration stage using hollow fiber filtration membranes; 3) performing ultrafiltration and dialysis tests using tangential flow and hollow fiber filtration systems, ensuring the concentration and purification of HA; 4) implementing chromatographic processes with columns loaded with activated charcoal and silica, optimizing product purification; 5) testing and optimizing HA drying using spray drying and lyophilization; 6) establishing production conditions in compliance with good laboratory practices (GLP-like), ensuring the quality of the final product; and 7) conducting tests in 1000 L bioreactors, advancing to Technology Readiness Level (TRL) 9. The expected results include the commercial validation and scaling up of production processes to larger volumes, providing high-quality and purity HA ready for health product applications. The necessary resources include specialized equipment, reagents, appropriate infrastructure for scaling up, and a team of qualified professionals. The anticipated commercial impact includes positioning BIOBREYER as a reference in sustainable HA production, increasing its market competitiveness, and meeting significant demand with an excellent national product. The successful execution of this project will strengthen BIOBREYER's position in the biotechnology market, opening new business opportunities and contributing to innovation in the bioproducts sector. (AU)