Combined in silico modeling and metabolomics analysis to characterize fed-batch CHO cell culture.

The increasing demand for recombinant therapeutic proteins highlights the need to constantly improve the efficiency and yield of these biopharmaceutical products from mammalian cells, which is fully achievable only through proper understanding of cellular functioning. Towards this end, the current study exploited a combined metabolomics and in silico modeling approach to gain a deeper insight into the cellular mechanisms of Chinese hamster ovary (CHO) fed-batch cultures. Initially, extracellular and intracellular metabolite profiling analysis shortlisted key metabolites associated with cell growth limitation within the energy, glutathione, and glycerophospholipid pathways that have distinct changes at the exponential-stationary transition phase of the cultures.

Genome-scale modeling and in silico analysis of ethanologenic bacteria Zymomonas mobilis.

Bioethanol has been recognized as a potential alternative energy source. Among various ethanol-producing microbes, Zymomonas mobilis has acquired special attention due to its higher ethanol yield and tolerance. However, cellular metabolism in Z.

Combined data preprocessing and multivariate statistical analysis characterizes fed-batch culture of mouse hybridoma cells for rational medium design.

We present an integrated framework for characterizing fed-batch cultures of mouse hybridoma cells producing monoclonal antibody (mAb). This framework systematically combines data preprocessing, elemental balancing and statistical analysis technique. Initially, specific rates of cell growth, glucose/amino acid consumptions and mAb/metabolite productions were calculated via curve fitting using logistic equations, with subsequent elemental balancing of the preprocessed data indicating the presence of experimental measurement errors.

Genome-scale metabolic reconstruction and in silico analysis of methylotrophic yeast Pichia pastoris for strain improvement.

Background: Pichia pastoris has been recognized as an effective host for recombinant protein production. A number of studies have been reported for improving this expression system. However, its physiology and cellular metabolism still remained largely uncharacterized.

Genome-scale modeling and in silico analysis of mouse cell metabolic network.

Genome-scale metabolic modeling has been successfully applied to a multitude of microbial systems, thus improving our understanding of their cellular metabolisms. Nevertheless, only a handful of works have been done for describing mammalian cells, particularly mouse, which is one of the important model organisms, providing various opportunities for both biomedical research and biotechnological applications. Presented herein is a genome-scale mouse metabolic model that was systematically reconstructed by improving and expanding the previous generic model based on integrated biochemical and genomic data of Mus musculus.

Elucidation of metabolism in hybridoma cells grown in fed-batch culture by genome-scale modeling.

Genome-scale modeling of mouse hybridoma cells producing monoclonal antibodies (mAb) was performed to elucidate their physiological and metabolic states during fed-batch cell culture. Initially, feed media nutrients were monitored to identify key components among carbon sources and amino acids with significant impact on the desired outcome, for example, cell growth and antibody production. The monitored profiles indicated rapid assimilation of glucose and glutamine during the exponential growth phase.

Characterizing Escherichia coli DH5alpha growth and metabolism in a complex medium using genome-scale flux analysis.

Genome-scale flux analysis of Escherichia coli DH5alpha growth in a complex medium was performed to investigate the relationship between the uptake of various nutrients and their metabolic outcomes. During the exponential growth phase, we observed a sequential consumption order of serine, aspartate and glutamate in the complex medium as well as the complete consumption of key carbohydrate nutrients, glucose and trehalose. Based on the consumption and production rates of the measured metabolites, constraints-based flux analysis of a genome-scale E.