Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development

doi:10.1016/j.cjche.2018.10.009

中国化学工程学报 ›› 2019, Vol. 27 ›› Issue (5): 1171-1176.DOI: 10.1016/j.cjche.2018.10.009

• Biotechnology and Bioengineering • 上一篇下一篇

Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development

Lijuan Shen¹, Xu Yan¹, Lei Nie^1,2, Wenyan Xu², Shiwei Miao², Haibin Wang², H. Fai Poon², Haibin Qu¹

1 Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China;
2 Zhejiang Hisun Pharmaceutical Co., Ltd., Fuyang, Hangzhou 311404, China

收稿日期:2018-08-09 修回日期:2018-09-26 出版日期:2019-05-28 发布日期:2019-06-27
通讯作者: Haibin Qu
基金资助:
Supported by the Science and Technology Development Program of Zhejiang Province (2017C03003).

Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development

Lijuan Shen¹, Xu Yan¹, Lei Nie^1,2, Wenyan Xu², Shiwei Miao², Haibin Wang², H. Fai Poon², Haibin Qu¹

1 Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China;
2 Zhejiang Hisun Pharmaceutical Co., Ltd., Fuyang, Hangzhou 311404, China

Received:2018-08-09 Revised:2018-09-26 Online:2019-05-28 Published:2019-06-27
Contact: Haibin Qu
Supported by:
Supported by the Science and Technology Development Program of Zhejiang Province (2017C03003).

摘要/Abstract

摘要： A deeper understanding of the biological events occurring when bioprocess parameters changed will be of great value in improving the monoclonal antibodies (mAbs) production. Design of experiment (DoE) was applied to investigate the effect of process parameters (pH, temperature shift and dissolve oxygen (DO)) on protein titer. The key metabolites connecting the critical process parameters (CPPs) with monoclonal antibody production were identified by different chemometrics tools. Finally, the biological events of marker metabolites relating with titer improvement were concluded. pH and temperature shift were identified as CPPs that affect the target protein titer. A series of metabolites influenced by the altered CPPs and correlated with protein titer were screened by principal component analysis (PCA) and Pearson' correlation test. The marker metabolites and their pathways linking CPPs to target protein titer in different culture phases were summarized. Metabolomics and chemometrics are promising data-driven tools to shine light into the biological black box between the bioprocess parameters and process performance.

关键词: Canonical metabolites, Chemometrics, Critical process parameters, Metabolomics, Protein titer

Abstract: A deeper understanding of the biological events occurring when bioprocess parameters changed will be of great value in improving the monoclonal antibodies (mAbs) production. Design of experiment (DoE) was applied to investigate the effect of process parameters (pH, temperature shift and dissolve oxygen (DO)) on protein titer. The key metabolites connecting the critical process parameters (CPPs) with monoclonal antibody production were identified by different chemometrics tools. Finally, the biological events of marker metabolites relating with titer improvement were concluded. pH and temperature shift were identified as CPPs that affect the target protein titer. A series of metabolites influenced by the altered CPPs and correlated with protein titer were screened by principal component analysis (PCA) and Pearson' correlation test. The marker metabolites and their pathways linking CPPs to target protein titer in different culture phases were summarized. Metabolomics and chemometrics are promising data-driven tools to shine light into the biological black box between the bioprocess parameters and process performance.

Key words: Canonical metabolites, Chemometrics, Critical process parameters, Metabolomics, Protein titer

Lijuan Shen, Xu Yan, Lei Nie, Wenyan Xu, Shiwei Miao, Haibin Wang, H. Fai Poon, Haibin Qu. Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development[J]. 中国化学工程学报, 2019, 27(5): 1171-1176.

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Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development

Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development

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