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Metabolism and metabolic burden by α1-antitrypsin production in human AGE1.HN cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
31599 44823 2013 12 PDF Available
Title
Metabolism and metabolic burden by α1-antitrypsin production in human AGE1.HN cells
Abstract

The metabolic burden on human AGE1.HN cells imposed by the production of recombinant α1-antitrypsin (A1AT) was studied by comparing a selected high-producing clonal cell line with the parental cell line. RNA, lipid, and phosphatidylcholine fractions were higher in the producer cell line causing metabolic changes in the producer, e.g., increased glycine and glutamate production. By simulating the theoretical metabolite demand for production of mature A1AT using a network model, it was found that the differences in metabolic profiles between producer and parental cells match the observed increased C1-unit and nucleotide demand as well as lipid precursor demand in the producer. Additionally, metabolic flux analysis revealed similar energy metabolism in both cell lines. The increased lipid content seems related to activated secretion machinery in the producer cell line. Increased lipid and C1 metabolism seem important targets for further improvement of AGE1.HN and other producing mammalian cells.

► New human cell line AGE1.HN produces fully human type α1-antitrypsin. ► Higher RNA and lipid content is typical for production and secretion of human α1-antitrypsin. ► In silico network analysis and metabolic flux analysis point to the same targets for improvement. ► Identified metabolic targets for α1-antitrypsin production are mainly C1 and lipid metabolism. ► This may be implemented by genetic engineering or by applying useful feeding strategies.

Keywords
Mammalian cell; Cell culture; Biopharmaceutical; Metabolic flux; AAT deficiency; Therapeutic protein
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Metabolism and metabolic burden by α1-antitrypsin production in human AGE1.HN cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 16, March 2013, Pages 103–114
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us