TAG: GS 3: SCIENCE AND TECHNOLOGY
THE CONTEXT: Researchers at the Indian Institute of Science (IISc) in the Department of Biochemistry have developed an innovative method for the mass production of recombinant proteins.
EXPLANATION:
- This method utilizes a common food additive, monosodium glutamate (MSG), as an alternative to methanol, traditionally used in yeast cell factories.
- The novel approach promises to be safer and more efficient, paving the way for its application in various biotechnological industries.
What are Recombinant Proteins?
- Recombinant proteins are proteins encoded by recombinant DNA that has been cloned in a system that supports the expression of the gene and translation of mRNA.
- These proteins include crucial substances such as vaccine antigens, insulin, and monoclonal antibodies.
- They are essential in medical treatments, diagnostics, and research.
- Traditionally, recombinant proteins are produced by growing modified bacterial, viral, or mammalian cells in large bioreactors.
- The yeast Pichia pastoris (now called Komagataella phaffii) is widely used for this purpose due to its ability to grow to high cell densities and its capability to perform post-translational modifications.
- The production process involves the use of a unique promoter within the yeast genome, which is activated by methanol.
- This promoter codes for an enzyme called alcohol oxidase (AOX).
- The gene coding for the desired recombinant protein is inserted next to the AOX promoter.
- Initially, yeast cells are grown using glycerol or glucose as the carbon source.
- Once a sufficient cell mass is achieved, methanol is introduced to activate the AOX promoter, leading to the production of the recombinant protein in large quantities.
Challenges with Methanol
- Methanol is highly flammable and hazardous, necessitating stringent safety measures in industrial settings.
- Its handling requires careful attention to prevent fire hazards and accidents.
- Methanol metabolism produces hydrogen peroxide, which can cause oxidative stress in yeast cells and potentially damage the recombinant proteins.
- This can lead to reduced yields and compromised protein quality.
The Novel Method Developed by IISc
- To address the issues associated with methanol, a former PhD student at IISc, along with her team, explored various alternatives.
- Their research identified monosodium glutamate (MSG) as a viable substitute.
- MSG is a USFDA-approved food additive commonly used to enhance flavor in foods.
- The researchers discovered that MSG activates a different promoter within the yeast genome that codes for the enzyme phosphoenolpyruvate carboxykinase (PEPCK).
- By activating the PEPCK promoter with MSG, they could induce protein production similarly to the methanol-induced AOX promoter.
Advantages of the MSG-Based Method
- MSG is non-flammable and poses significantly fewer risks compared to methanol.
- Its use eliminates the need for stringent safety precautions associated with methanol, making the production process safer and more manageable.
- Unlike methanol, MSG does not produce harmful byproducts like hydrogen peroxide.
- This reduces the oxidative stress on yeast cells and minimizes the risk of damage to the recombinant proteins, potentially improving yield and quality.
Potential Applications
- The IISc researchers are optimistic that this novel expression system can be widely adopted in biotech industries for the mass production of various valuable proteins.
- These include:
- Therapeutic Proteins: Production of insulin, monoclonal antibodies, and other therapeutic molecules.
- Nutraceuticals: Proteins for dietary supplements, including milk and egg proteins.
- Baby Food Supplements: High-quality proteins to enhance the nutritional value of baby foods.