Process For Production Of High Molecular Weight Hyaluronan In A Recombinant Lactococcus Lactis Using Acetate Co-utilization Fed-batch Strategy
Categories for this Invention
Biotechnology & Genetic Engineering
Industry: Pharmaceuticals, Biomedical Products
Applications: Advanced Materials, Food & Drugs, Medical & Surgical, Medical-grade hyaluronic acid (HA) for visco-supplementation in osteoarthritis treatment, High MWHA for enhanced stability in eye surgeries, HA in wound healing applications, HA for anti-cancer drug delivery, Cosmetic applications utilizing low molecular weight HA.
Market: The Global Hyaluronic Acid Market was estimated at USD 1.1 Bn in 2021, is expected to reach around USD 2.60 Bn by 2030, growing at 8% CAGR from 2022 to 2030.
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Problem Statement
- Current methods for hyaluronic acid (HA) production suffer from limitations like lower molecular weights, hindering effectiveness in biomedical applications.
- Existing metabolic engineering approaches focus on enzyme-coding genes but often overlook crucial cofactors, impacting HA production in recombinant strains like L. lactis.
- Traditional methods and past engineering efforts left an unmet need for higher molecular weight HA demand in medical applications.
- Utilization of cost-effective acetate in HA production faces challenges, there is a critical gap in exploring cofactor engineering strategies to enhance HA production and achieve greater stability for biomedical uses.
- Hence, there lies a need for enhancing MWHA production, using process strategies, especially with acetate supplementation and co-utilization.
- The instant invention discloses a process for producing higher MWHA (3.4 MDa) with high yield by anaerobic microbial fermentation with process control parameters.
Technology
- Utilization of a genetically engineered strain of Lactococcus lactis, named MKG6, expressing key genes from Streptococcus zooepidemicus for enhanced HA biosynthesis.
- Strategically manipulating metabolic pathways (FIG 2) and introduces acetate co-utilization to optimize cofactors like acetyl-CoA, crucial for HA production.
- Incorporating batch acetate pulse feed, batch process with acetate and glucose pulse feed, constant fed-batch, and pH feedback fed-batch strategies for controlled & sustained HA production.
- The invention introduces a process for producing hyaluronic acid (HA) with a consistently high molecular weight (3.4 MDa) through anaerobic microbial fermentation. The process comprises:
Key Features / Value Proposition
User perspective:
- Enhanced Product Efficacy, Improved product Stability which is critical for reliable outcomes in medical treatments.
- Versatile Applications, including osteoarthritis treatment, eye surgeries, wound healing, anti-cancer drug delivery, and cosmetics.
- Biocompatibility with reduced immunogenicity and non-toxicity. Advanced Healthcare Solutions for various medical conditions.
Industrial perspective:
- Cost-Effective Production, Breakthrough Technology achieving MWHA of 3.4 MDa.
- Market Leadership and Bioprocessing Innovation with novel fermentation strategies.
- Implement advanced fed-batch fermentation processes, including acetate pulse feed and pH feedback, for sustained high MWHA.
Technology perspective:
- Employ cutting-edge genetic engineering techniques for recombinant L. lactis MKG6, enhancing HA pathway expression.
- Strategically manipulate metabolic fluxes to maximize precursor availability and HA production. Introduce acetate co-utilization to optimize acetyl-CoA levels, a key cofactor in HA biosynthesis.
- Leverage in-silico flux balance analysis to understand and optimize intracellular fluxes, influencing HA production.
Questions about this Technology?
Contact For Licensing
sm-marketing@imail.iitm.ac.in
ipoffice2@iitm.ac.in
Research Lab
Prof. Prabhu Rajagopal
Department of Mechanical EngineeringÂ
Intellectual Property
IITM IDF No.: 1862
 IP No.: 412658 (Granted)
PCT Application No. PCT/IN2020/050447
Technology Readiness Level
TRL-4
Validated in Laboratory