Inducible engineering precursor metabolic flux for synthesizing hyaluronic acid of customized molecular weight in Streptococcus zooepidemicus.
Summary
The authors engineered an endogenous expression toolkit (32 constitutive, 4 inducible elements) in S. zooepidemicus to modulate hasE and balance HA precursors, enabling one-step fermentation of HA with tunable molecular weights. A sucrose-inducible system allowed precise MW control from 0.78 to 1.77 MDa, with promoter strength correlating positively with MW.
Key Findings
- hasE transcription level positively correlates with HA molecular weight in S. zooepidemicus.
- Promoter engineering yielded HA of 1.96 MDa (strong PR31) vs 1.63 MDa (weaker PR22).
- A sucrose-inducible expression system enabled precise MW tuning from 0.78 to 1.77 MDa.
- Oversupply of either UDP-GlcNAc or UDP-GlcA reduces HA molecular weight, highlighting precursor balance.
Clinical Implications
While preclinical, customizable HA MW can inform selection/design of dermal fillers, viscoelastic injectables, and topical formulations to match desired bioactivity and residence time.
Why It Matters
This mechanistic bioprocess innovation enables tailored HA molecular weights critical for cosmetic fillers, ophthalmology, and regenerative products, potentially lowering costs and improving consistency.
Limitations
- Laboratory-scale demonstration without industrial scale-up metrics (yield, productivity, robustness).
- No evaluation of bioburden, endotoxin, or clinical-grade quality attributes for downstream cosmetic/medical use.
Future Directions
Scale-up fermentation studies with process control, life-cycle and cost analyses, and mapping MW to functional performance in dermal fillers and topical formulations.
Study Information
- Study Type
- Case series
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical experimental laboratory study demonstrating mechanistic control of product attributes.
- Study Design
- OTHER