Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Cell metabolism can vary considerably over the course of a typical fed-batch antibody production process. However, the intracellular pathway alterations associated with various phases of growth and antibody production have yet to be fully elucidated using industrially relevant production hosts. Therefore, we performed (13)C labeling experiments and metabolic flux analysis (MFA) to characterize CHO cell metabolism during four separate phases of a fed-batch culture designed to closely represent industrial process conditions. First, we found that peak specific growth rate was associated with high lactate production and minimal TCA cycling. Conversely, we found that lactate metabolism switched from net production to net consumption as the culture transitioned from peak growth to peak antibody production. During the peak antibody production phase, energy was primarily generated through oxidative phosphorylation, which was also associated with elevated oxidative pentose phosphate pathway (oxPPP) activity. Interestingly, as TCA cycling and antibody production reached their peaks, specific growth rate continued to diminish as the culture entered stationary phase. However, TCA cycling and oxPPP activity remained high even as viable cell density began to decline. Overall, we found that a highly oxidative state of metabolism corresponded with peak antibody production, whereas peak cell growth was characterized by a highly glycolytic metabolic state.
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Source |
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http://dx.doi.org/10.1002/bit.24858 | DOI Listing |
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