{"title":"Bioprocess biomarker identification and diagnosis for industrial mAb production based on metabolic profiling and multivariate data analysis.","authors":"Yingting Shi, Yuxiang Wan, Jiayu Yang, Yuting Lu, Xinyuan Xie, Jianyang Pan, Haibin Wang, Haibin Qu","doi":"10.1007/s00449-025-03142-4","DOIUrl":null,"url":null,"abstract":"<p><p>Monoclonal antibody (mAb) production is a complex bioprocess influenced by various cellular and metabolic factors. Understanding these interactions is critical for optimizing manufacturing and improving yields. In this study, we proposed a diagnostic and identification strategy using quantitative proton nuclear magnetic resonance (<sup>1</sup>H qNMR) technology-based pharmaceutical process-omics to analyze bioprocess variability and unveil significant metabolites affecting cell growth and yield during industrial mAb manufacturing. First, batch level model (BLM) and orthogonal partial least squares-discriminant analysis (OPLS-DA) identified glucose and lactate as primary contributors to culture run variability. Maintaining an optimal glucose set point was crucial for high-yield runs. Second, a partial least squares (PLS) regression model was established, which revealed viable cell density (VCD), along with glutamine, maltose, tyrosine, citrate, methionine, and lactate, as critical variables impacting mAb yield. Finally, hierarchical clustering analysis (HCA) highlighted one-carbon metabolism metabolites, such as choline, pyroglutamate, and formate, as closely associated with VCD. These findings provide a foundation for future bioprocess optimization through cell line engineering and media formulation adjustments, ultimately enhancing mAb production efficiency.</p>","PeriodicalId":9024,"journal":{"name":"Bioprocess and Biosystems Engineering","volume":" ","pages":"771-783"},"PeriodicalIF":3.5000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioprocess and Biosystems Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s00449-025-03142-4","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Monoclonal antibody (mAb) production is a complex bioprocess influenced by various cellular and metabolic factors. Understanding these interactions is critical for optimizing manufacturing and improving yields. In this study, we proposed a diagnostic and identification strategy using quantitative proton nuclear magnetic resonance (1H qNMR) technology-based pharmaceutical process-omics to analyze bioprocess variability and unveil significant metabolites affecting cell growth and yield during industrial mAb manufacturing. First, batch level model (BLM) and orthogonal partial least squares-discriminant analysis (OPLS-DA) identified glucose and lactate as primary contributors to culture run variability. Maintaining an optimal glucose set point was crucial for high-yield runs. Second, a partial least squares (PLS) regression model was established, which revealed viable cell density (VCD), along with glutamine, maltose, tyrosine, citrate, methionine, and lactate, as critical variables impacting mAb yield. Finally, hierarchical clustering analysis (HCA) highlighted one-carbon metabolism metabolites, such as choline, pyroglutamate, and formate, as closely associated with VCD. These findings provide a foundation for future bioprocess optimization through cell line engineering and media formulation adjustments, ultimately enhancing mAb production efficiency.
期刊介绍:
Bioprocess and Biosystems Engineering provides an international peer-reviewed forum to facilitate the discussion between engineering and biological science to find efficient solutions in the development and improvement of bioprocesses. The aim of the journal is to focus more attention on the multidisciplinary approaches for integrative bioprocess design. Of special interest are the rational manipulation of biosystems through metabolic engineering techniques to provide new biocatalysts as well as the model based design of bioprocesses (up-stream processing, bioreactor operation and downstream processing) that will lead to new and sustainable production processes.
Contributions are targeted at new approaches for rational and evolutive design of cellular systems by taking into account the environment and constraints of technical production processes, integration of recombinant technology and process design, as well as new hybrid intersections such as bioinformatics and process systems engineering. Manuscripts concerning the design, simulation, experimental validation, control, and economic as well as ecological evaluation of novel processes using biosystems or parts thereof (e.g., enzymes, microorganisms, mammalian cells, plant cells, or tissue), their related products, or technical devices are also encouraged.
The Editors will consider papers for publication based on novelty, their impact on biotechnological production and their contribution to the advancement of bioprocess and biosystems engineering science. Submission of papers dealing with routine aspects of bioprocess engineering (e.g., routine application of established methodologies, and description of established equipment) are discouraged.