title: Optimizing eukaryotic cell hosts for protein production through systems biotechnology and genome-scale modeling.
abstract: Eukaryotic cell lines, including Chinese hamster ovary cells, yeast, and insect cells, are invaluable hosts for the production of many recombinant proteins. With the advent of genomic resources, one can now leverage genome-scale computational modeling of cellular pathways to rationally engineer eukaryotic host cells. Genome-scale models of metabolism include all known biochemical reactions occurring in a specific cell. By describing these mathematically and using tools such as flux balance analysis, the models can simulate cell physiology and provide targets for cell engineering that could lead to enhanced cell viability, titer, and productivity. Here we review examples in which metabolic models in eukaryotic cell cultures have been used to rationally select targets for genetic modification, improve cellular metabolic capabilities, design media supplementation, and interpret high-throughput omics data. As more comprehensive models of metabolism and other cellular processes are developed for eukaryotic cell culture, these will enable further exciting developments in cell line engineering, thus accelerating recombinant protein production and biotechnology in the years to come.
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA, USA.|Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Jahir M
authors.initials: JM
authors.lastname: Gutierrez
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, San Diego, CA, USA. nlewisres@ucsd.edu.|Department of Pediatrics, University of California, San Diego, CA, USA. nlewisres@ucsd.edu.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
mesh_terms: D000818:Animals; D016466:CHO Cells; D060846:Cell Engineering; D006224:Cricetinae; D003412:Cricetulus; D016678:Genome; D006801:Humans; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D011994:Recombinant Proteins
keywords: Eukaryotic cell engineering; Genome-scale models; Metabolic networks; Recombinant protein production; Systems Biology