Hyaluronic Acid (Hyaluronan) Engineering Service

Hyaluronic Acid (HA), or Hyaluronan, is a high-value polysaccharide essential in cosmetics (moisturizing), orthopedics (viscosupplementation), and ophthalmology. The traditional method of animal extraction often results in low purity and raises safety concerns due to potential co-purified proteins. While microbial fermentation is a safer alternative, it frequently produces HA with an uneven molecular weight (MW) distribution , making it difficult to achieve the specific MW ranges required for different medical and cosmetic applications.

CD Biosynsis offers a synthetic biology service focused on the Streptococcus chassis. Our core strategy involves the modification of hyaluronic acid synthase (HAS) in Streptococcus to enhance its catalytic efficiency and potentially regulate chain elongation. This is complemented by the regulation of molecular weight under fermentation conditions , achieved through media component tuning and precise control of HAS expression. This integrated approach aims to deliver high-purity, safe, and custom MW HA for specialized market needs.

Pain Points

The supply of high-quality HA faces these critical bioengineering and safety challenges:

• Low Purity of Animal Extraction: Extraction from rooster combs or other animal tissues yields HA contaminated with unwanted proteins and nucleic acids , requiring extensive and costly purification.
• Molecular Weight Heterogeneity: Microbial HA often features an uneven molecular weight distribution , which is a major issue since function (e.g., cell penetration, viscosity) is MW-dependent.
• Safety and Regulatory Concerns: Animal sources carry inherent risks of viral transmission or immune reactions . Recombinant production offers a safer path but demands strict purity control.
• Precursor Supply Limitations: Efficient HA synthesis requires a high and balanced supply of two sugar precursors (UDP-GlcNAc and UDP-GlcA), which can be a metabolic bottleneck .

An effective solution must ensure biological safety and provide precise control over the final product's molecular structure.

Solutions

CD Biosynsis utilizes advanced synthetic biology to control the HA chain elongation process:

Modification of Hyaluronic Acid Synthase (HAS) in Streptococcus

           

We employ directed evolution and rational design to modify the HAS enzyme to tune its polymerization rate and potentially its ability to control chain termination, targeting specific MW ranges.

Regulation of Molecular Weight under Fermentation Conditions

We fine-tune key parameters like initial precursor concentrations, pH, and specific ion levels during fermentation, which are known to influence HAS activity and final HA MW.

Precursor Metabolism Engineering

We modify the host's pathway to enhance the supply and balance of UDP-GlcNAc and UDP-GlcA, ensuring adequate building blocks for high-rate, high-MW polymerization.

Antidegradation Strategy

We introduce mutations or environmental controls to minimize the activity of host hyaluronidases and other degradative enzymes that could break down the high-MW product.

This systematic approach is focused on delivering a safer and structurally tailored HA product through precise fermentation control.

Advantages

Our HA engineering service is dedicated to pursuing the following production goals:

High Purity and Safety

Microbial fermentation eliminates animal-derived contaminants, providing a safer, purer product with clear regulatory benefits.

Custom Molecular Weight Control

The ability to precisely tune the MW allows for the creation of specific HA products tailored for injection (high MW) or topical use (low MW).

Enhanced Biosynthesis Efficiency

Modification of the HAS and precursor pathways aims to increase the specific productivity of the host strain.

Scalability and Consistency

Microbial fermentation offers a highly scalable and consistent manufacturing process independent of animal sourcing variations.

Cost Reduction Potential

High yield and reduced downstream purification complexity are focused on lowering the overall cost of the final product. [Image of Cost Reduction Icon]

We provide a biosynthetic platform aimed at overcoming the safety and molecular structure challenges of HA production.

Process

Our HA strain engineering service follows a standardized, multi-stage research workflow:

• HAS Engineering: Apply high-throughput screening of HAS variants to select enzymes with optimized polymerization rates and improved processivity.
• Precursor Pathway Tuning: Overexpress key enzymes involved in the synthesis of UDP-GlcNAc and UDP-GlcA to eliminate metabolic bottlenecks.
• Host Genome Stabilization: Knock out or downregulate genes for hyaluronidases to protect the high-MW HA product from degradation during and after synthesis.
• Fermentation Parameter Screening: Systematically screen and optimize fermentation conditions (pH, temperature, substrate concentration, ion concentration) to establish a clear MW control map .
• Scale-Up and MW Validation: Test the final engineered strain in fed-batch fermentation, precisely measuring the final titer and average molecular weight using gel permeation chromatography (GPC).
• Result Report Output: Compile a comprehensive Experimental Report detailing HAS modification data, metabolic flux data, and final titer/MW/purity assessment , supporting specialized product development.

Technical communication is maintained throughout the process, focusing on timely feedback regarding HA molecular weight and productivity.

Explore the potential for custom-MW, high-purity HA production. CD Biosynsis provides customized strain engineering solutions:

• Detailed Molecular Weight Distribution Analysis Report , demonstrating the precision of MW control and homogeneity.
• Consultation on fermentation strategies optimized for specific MW targets.
• Experimental reports include complete raw data on titer, purity, and HA degradation rates , essential for product stability assessment.