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

Lijuan Shen; Xu Yan; Lei Nie; Wenyan Xu; Shiwei Miao; Haibin Wang; H. Fai Poon; Haibin Qu

doi:10.1016/j.cjche.2018.10.009

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

Biotechnology and Bioengineering | Updated：2026-01-06

- 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
- 中国化学工程学报（英文版） 2019年27卷第5期页码：1171-1176
- Affiliations：
  
  1. Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University,Hangzhou,China,310058
  2. Zhejiang Hisun Pharmaceutical Co., Ltd.,, Hangzhou,Fuyang,China,311404
- Author bio：
- Funds：
- DOI：10.1016/j.cjche.2018.10.009
  中图分类号：
- 纸质出版：2019
- Accepted：
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Lijuan Shen, Xu Yan, Lei Nie, 等. 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（英文版）, 2019,27(5):1171-1176.

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]. Chinese Journal of Chemical Engineering, 2019, 27(5): 1171-1176.
Lijuan Shen, Xu Yan, Lei Nie, 等. 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（英文版）, 2019,27(5):1171-1176. DOI： 10.1016/j.cjche.2018.10.009.

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]. Chinese Journal of Chemical Engineering, 2019, 27(5): 1171-1176. DOI： 10.1016/j.cjche.2018.10.009.

摘要

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.

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