“…Although human-derived cell lines benefit from the ability to generate human PTMs, challenges still remain, such as increasing the protein production titer (Chin et al, 2019;Dietmair et al, 2012;Mori et al, 2020) and creating a genetic engineering toolbox with specialized tools for human cells (Xu and Qi 2019). Recent publications have pursued some of these challenges, including the aim to increase the protein production and secretion power either by cell-line development approaches (Chin et al, 2019;Rahimpour et al, 2013) or cell culture process optimization (Schwarz et al, 2019), as well as to increase the quality of the secreted proteins by engineering folding and PTM pathways (Meuris et al, 2014;Del Val et al, 2016;Liang et al, 2020;Behrouz et al, 2020). However, despite the current knowledge of protein production and secretion in eukaryotic cells, there is still notable ambiguity in understanding and predicting the production and secretion rates as well as product quality under different conditions (Kafri et al, 2016;Liu et al 2016).…”