10x higher yield for BLG production: Innovation by Real Deal Milk
DAIRY & ALTERNATIVES SUSTAINABILITYALTERNATIVE PROTEINS
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The Spain-based startup Real Deal Milk has filed a patent application for a recombinant fusion protein that promises to transform the production of high-value proteins used in food, agriculture, and medicine. By leveraging caseinomacropeptide (CMP), a fragment of milk protein κ-casein, the invention significantly enhances the yield and efficiency of recombinant protein expression—addressing a major bottleneck in precision fermentation and synthetic biology.
The Challenge: Low Yields in Recombinant Protein Production
Recombinant proteins—produced by genetically modified microorganisms—are widely used in industries ranging from food to pharmaceuticals. However, many proteins suffer from low expression yields in heterologous host systems, making large-scale production economically unviable. Traditional approaches to boost yields, such as optimizing promoters or fermentation conditions, often fall short for certain proteins, particularly milk proteins like β-lactoglobulin (BLG).
Real Deal Milk’s Solution: Fusion with Caseinomacropeptide (CMP)
The patent application (EP4545556A1) describes a fusion protein system where a target protein (e.g., BLG) is linked to CMP, a highly hydrophilic peptide derived from κ-casein. Surprisingly, this fusion dramatically increases protein yield—sometimes by more than 10-fold—compared to expressing the target protein alone.
Key Advantages of the CMP Fusion Technology:
Enhanced Hydrophilicity & Solubility – CMP’s hydrophilic nature improves protein stability and secretion.
Higher Titers – Fusion proteins achieve far greater yields than standalone proteins under identical conditions.
Scalable & Sustainable – Reduces reliance on animal agriculture, lowering environmental impact.
Cleavable Linkers – The fusion protein can be enzymatically split (e.g., using chymosin or enteropeptidase) to recover the target protein in pure form.
Applications: From Dairy Alternatives to Therapeutics
The technology is particularly impactful for:
Alternative Dairy Products – High-yield production of BLG, caseins, and other milk proteins for plant-based milk, cheese, and yogurt.
Nutritional Supplements – Efficient synthesis of whey proteins for sports and clinical nutrition.
Pharmaceuticals – Improved yields of therapeutic proteins, enzymes, and antibodies.
Experimental Validation
Real Deal Milk’s data shows:
BLG-CMP fusion proteins express at 11-16 times higher levels than BLG alone.
Casein-CMP fusions also see dramatic yield improvements compared to native caseins.
The system works in yeast (Pichia pastoris), a preferred host for industrial protein production.
Conclusion: A Game-Changer for Precision Fermentation
Real Deal Milk’s patented CMP fusion technology solves a critical challenge in recombinant protein manufacturing, paving the way for cost-effective, sustainable, and high-yield production of essential proteins. This innovation could accelerate the shift from animal-derived proteins to fermentation-based alternatives, benefiting both industry and the environment.
