کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6452668 1361476 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Application of 13C flux analysis to identify high-productivity CHO metabolic phenotypes
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Application of 13C flux analysis to identify high-productivity CHO metabolic phenotypes
چکیده انگلیسی


- 13C flux analysis was used to identify phenotypes associated with high IgG production.
- High-producers exhibited lactate uptake and elevated CAC flux in stationary phase.
- Bcl-2Δ overexpression enhanced glucose oxidation and IgG production in most clones.

Industrial bioprocesses place high demands on the energy metabolism of host cells to meet biosynthetic requirements for maximal protein expression. Identifying metabolic phenotypes that promote high expression is therefore a major goal of the biotech industry. We conducted a series of 13C flux analysis studies to examine the metabolic response to IgG expression during early stationary phase of CHO cell cultures grown in 3 L fed-batch bioreactors. We examined eight clones expressing four different IgGs and compared with three non-expressing host-cell controls. Some clones were genetically manipulated to be apoptosis-resistant by expressing Bcl-2Δ, which correlated with increased IgG production and elevated glucose metabolism. The metabolic phenotypes of the non-expressing, IgG-expressing, and Bcl-2Δ/IgG-expressing clones were fully segregated by hierarchical clustering analysis. Lactate consumption and citric acid cycle fluxes were most strongly associated with specific IgG productivity. These studies indicate that enhanced oxidative metabolism is a characteristic of high-producing CHO cell lines.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolic Engineering - Volume 43, Part B, September 2017, Pages 218-225
نویسندگان
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