A Fast Method to Reduce Ammonium and Lactic Acid Production in Industrial Animal Cell Cultures

Albert Cwas^*
*Correspondence: Albert Cwas, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695, USA, Email:

Keywords

Cell culture • By-products • Ammonium

Introduction

Industrial animal cell culture is essential for producing biopharmaceuticals, but it often leads to the accumulation of detrimental byproducts like ammonium and lactic acid. These byproducts can impair cell growth and reduce product yield. In this article, we examine a quick and effective approach to decrease the production of ammonium and lactic acid in industrial animal cell cultures. We focus on strategies such as using media additives, optimizing process conditions and exploring alternative culture techniques. Addressing the buildup of these byproducts is crucial, as ammonium can inhibit cell growth and lower product yield, while lactic acid, a byproduct of anaerobic metabolism, can acidify the culture medium and further challenge the efficiency and scalability of the process [1,2].

Literature Review

In this article, we explore strategies to minimize the production of byproducts such as ammonium and lactic acid in industrial animal cell culture. One effective method is to use media additives to modulate cellular metabolism. For instance, incorporating glutamine synthetase inhibitors like Methionine Sulfoximine (MSX) can decrease ammonium production by blocking the enzyme that converts glutamine to glutamate, which is a precursor to ammonium. Additionally, adding sodium bicarbonate or sodium hydroxide can neutralize lactic acid and prevent the acidification of the culture medium. Optimizing culture conditions is another crucial approach. Adjusting the pH of the culture medium to better match physiological levels can help reduce lactic acid accumulation. Fine-tuning the feeding strategy to deliver nutrients more precisely can also mitigate byproduct formation. Furthermore, optimizing cell density and agitation rates can enhance oxygen transfer, thereby decreasing lactic acid buildup [3,4].

Discussion

Alternative culture techniques, such as perfusion culture, can significantly reduce ammonium and lactic acid production. Perfusion culture involves the continuous removal of spent medium and its replacement with fresh medium. This process helps maintain a stable pH and prevents the buildup of harmful byproducts. Similarly, microcarrier-based culture systems can enhance oxygen transfer, which helps mitigate lactic acid accumulation. Ammonium is primarily produced through the deamination of amino acids, with glutamine being a major contributor. Although glutamine is a vital nutrient in cell culture, its metabolism generates ammonium, which can inhibit cell growth and productivity. Elevated ammonium levels can cause cellular stress, reduce protein synthesis and lead to cell death. Lactic acid is a byproduct of anaerobic glucose metabolism via glycolysis. In high-density cultures, oxygen becomes a limiting factor, leading cells to shift to anaerobic metabolism even when oxygen is available (a phenomenon known as the Warburg effect). This shift results in increased lactic acid production, which can acidify the culture medium. Acidification negatively affects enzyme activity, cell viability and overall product quality [5,6].

Conclusion

In conclusion, mitigating the production of ammonium and lactic acid in industrial animal cell culture is crucial for enhancing both the efficiency and scalability of biopharmaceutical manufacturing. Effective strategies include using media additives, optimizing culture conditions and employing alternative culture techniques. These approaches can significantly reduce the accumulation of these detrimental byproducts, thereby improving cell culture performance. Further advancements in technology and a deeper understanding of cellular metabolism will continue to refine our ability to control and optimize culture conditions. By optimizing nutrient concentrations, employing metabolic engineering, exploring alternative carbon sources, enhancing oxygen supply and refining bioreactor designs, we can achieve lower levels of unwanted metabolites. These improvements will contribute to more sustainable and productive biomanufacturing processes, paving the way for future innovations in cell culture technology.

Acknowledgement

None.

Conflict of Interest

There is no conflict of interest by author.

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