Luo J, et al., Comparative Metabolite Analysis to Understand Lactate Metabolism Shift in Chinese Hamster Ovary Cell Culture Process. Biotechnol Bioeng, 2011. 109(1): 146-56.
Metabolon results led to:
- A clear illustration that copper induces lactate consumption by increasing metabolic efficiency, thus providing a new strategy for controlling lactate in cell culture
- A new concept for selection of lactate-consuming clones based on mitochondrial properties
Key metabolomic observations:
- Elevated metabolic waste (pyruvate, sorbitol, lactate, and other glycolytic intermediates) in conditions not supplemented with copper
Chinese hamster ovary (CHO) cells are commonly used cells for biologics production but, as a by-product of metabolism, produce high concentrations of lactate that can result in poor culture performance. Investigators at Genentech discovered a positive correlation between copper and lactate suppression. In order to understand the molecular basis of lactate suppression by copper, metabolomics was performed. The results clearly showed that the cells with copper supplementation more efficiently used glucose and the final glycolytic product pyruvate. The data strongly inferred that this was due to more efficient oxidative metabolism. In addition to the results providing an important practical approach to controlling lactate metabolism in cell culture, they also suggest that the mitochondria may be an even more important organelle than previously appreciated. As such, the authors propose the idea that screening cell lines for favorable mitochondrial properties may be an important consideration for circumventing the introduction of lactogenic clones into development.