Amino acid metabolism, demand and supply in Chinese Hamster ovary cell culture – A comprehensive literature review

Chinese hamster ovary (CHO) cells serve as the predominant host for the production of recombinant protein biopharmaceuticals. Maintaining an optimal culture environment is critical to achieving high productivity, ensuring protein quality, and minimising production costs. Amino acids are a key component of cell culture media which are essential for promoting cell growth and protein expression. Amino acids are the fundamental building blocks of proteins and serve critical roles in cellular energy generation and biosynthesis. The demand for amino acids varies throughout batch or fed-batch culture, which necessitates careful media and process design to ensure adequate supplies. However, if oversupplied, certain amino acids and associated byproducts can negatively impact cell growth and protein production. This review consolidates our understanding of the complex role of amino acid metabolism in CHO cells in the context of industrial production systems and growth medium formulations. It identifies and discusses key considerations in the demand and supply of amino acids, including fed-batch dynamics, amino acid toxicity, solubility and stability, medium osmolality, amino acid transporters and the relative availability of different amino acids. Based on the synthesis of current knowledge, emerging strategies to balance amino acid supply with demand are discussed, and research priorities identified to advance future efforts to optimise CHO cell culture process and media formulation.