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

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

作者机构：Pharmaceutical Informatics InstituteCollege of Pharmaceutical ScienceZhejiang UniversityHangzhou 310058China Zhejiang Hisun Pharmaceutical Co.Ltd.FuyangHangzhou 311404China 

出 版 物：《Chinese Journal of Chemical Engineering》 (中国化学工程学报（英文版）)

年 卷 期：2019年第27卷第5期

页      面：1171-1176页

核心收录：

学科分类：0817[工学-化学工程与技术] 08[工学] 

基　　金：Supported by the Science and Technology Development Program of Zhejiang Province(2017C03003) 

主　　题：Canonical metabolites Chemometrics Critical process parameters Metabolomics Protein titer 

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.