While fed-batch processes remain state-of-the-art in the cell culture-based production of biopharmaceuticals, perfusion-based processes are increasingly being adopted to further increase productivity. Both process systems require concentrated media to replenish nutrients and avoid productivity loss caused by dilution. However, the solubility of amino acids can quickly become a limiting factor in the preparation of concentrated media. With a solubility of less than 0.5 g / liter in water at neutral pH, L-Tyrosine is especially challenging.

As L-Tyrosine is an important amino acid for protein synthesis and cellular metabolism, finding a solution to this solubility challenge can be critical to maximize process performance. As the solubility of L-Tyrosine increases when moving away from the isoelectric point,  a separate L-Tyrosine feed with an extreme pH has traditionally been used in addition to the main pH neutral feed . However, this approach faces many drawbacks, including increased process complexity, the risk of pH-spikes, the introduction of higher salt concentrations, and precipitation of L-Tyrosine when overdosing.

One approach that is being rapidly adopted by the industry is to overcome these challenges by replacing such amino acids with peptides. In order to increase solubility for free L-Tyrosine at a neutral pH, Evonik chemically couples L-Tyrosine to glycine via a peptide bond to create the peptide known as cQrex® GY (Glycyl-L-tyrosine dihydrate). Evonik’s cQrex® GY peptide delivers solubility that is high enough to prepare concentrated feeds without the need to modify pH. Indeed, the product can increase the solubility at neutral pH by up to 50 times compared to free L-Tyrosine. Because it can be efficiently taken up and metabolized by the cell, full replacement of L-Tyrosine becomes possible. Conversion to cQrex® GY as part of a single feed can significantly reduce process risk due to the resulting reduction in complexity. cQrex® GY has a strong record for quality and supply security to facilitate effective scale-up from lab to commercial volumes.

Like all cQrex® peptides and keto acids that can be used as supplements for the cultivation of animal and human cells, cQrex® GY is free of animal origin and chemically defined. A sample of cQrex® GY is available free from Evonik Health Care upon request. All cQrex® products are supplied as pure substances in crystalline form. Depending on the intended use, they can either be dissolved in water, a buffer of choice, or directly in the medium / feed. Recommendation on handling and formulation can also be provided on demand. To order a sample, email Evonik at healthcare@evonik.com.