ArticleCell systems2026
A community reconstruction of Chinese hamster metabolism and structural systems biology elucidate metabolic rewiring in lactate-free CHO cells.
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Article in Cell systems, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Improving recombinant protein productivity in CHO cells via multi-omics data integration.Bioresources and bioprocessing · 2026Review
- Toward a 4D genome annotation of CHO cells for biomanufacturing.Trends in biotechnology · 2026Review
- Selecting methods for draft GEM generation in multicellular eukaryotes: a comparative analysis.BMC bioinformatics · 2026Article
- Delineating the Transcriptional and Phenotypic Impact from Biotherapeutic Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Advancing recombinant protein production in CHO cells through metabolic engineering.Frontiers in bioengineering and biotechnology · 2026Review
- Wheels turning: CHO cell modeling moves into a digital biomanufacturing era: Subtitle: CHO Metabolic Modeling.Computational and structural biotechnology journal · 2025Review
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Authors and funding
41 authors.
Pablo Di GiustoDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 92093, USA; Center for Molecular Medicine, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Dong-Hyuk ChoiSchool of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Athanasios AntonakoudisSartorius Corporate Research, Royston SG8 5WY, UK.
Vikash Gokul DuraikannanDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India; Centre for Integrative Biology and Systems medicinE (IBSE), Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India.
Pierrick CraveurSartorius Corporate Research, 75000 Paris, France.
Nicholas Luke CowieNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
Tejaswini GanapathyDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India; Centre for Integrative Biology and Systems medicinE (IBSE), Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India.
Kannan RameshDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India.
Santiago Benavidez-LópezDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 Ciudad de México, México; Posgrado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, 04510 Ciudad de México, México.
Camila A OrellanaDepartment of Chemical and Bioprocess Engineering, School of Engineering, Pontificia Universidad Católica de Chile, 7820436 Santiago, Chile; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, 7820436 Santiago, Chile.
Natalia E JiménezDepartment of Chemical and Bioprocess Engineering, School of Engineering, Pontificia Universidad Católica de Chile, 7820436 Santiago, Chile; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, 7820436 Santiago, Chile.
Leo Alexander DworkinDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 92093, USA; Center for Molecular Medicine, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
James MorrisseyDepartment of Chemical Engineering, Imperial College London, London SW7 2AZ, UK.
Igor Marin de MasNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark; CAG Center for Endotheliomics, Copenhagen University Hospital, Righospitalet, 2100 Copenhagen, Denmark.
Benjamin StrainDepartment of Chemical Engineering, Imperial College London, London SW7 2AZ, UK.
Norma A Valdez-CruzDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 Ciudad de México, México; Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México 22800 Ensenada, Baja California, México.
Mauricio A Trujillo-RoldánDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 Ciudad de México, México; Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México 22800 Ensenada, Baja California, México.
Jannis MarzlufCorporate Research, Sartorius Stedim Cellca GmbH, 89081 Ulm, Germany; Department of Gene Therapy, University of Ulm, 89081 Ulm, Germany.
Verónica S MartínezAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
Leopold ZehetnerDepartment of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria.
Claudia AltamiranoEscuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, 2340000 Valparaíso, Chile; Centro Regional de Estudios en Alimentos Saludables, Curauma-Placilla, 2340000 Valparaíso, Chile; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, 7620086 Santiago, Chile; Center for Interdisciplinary Research in Biomedicine, Biotechnology and Well-Being (CID3B), Pontificia Universidad Católica de Valparaíso, 2340000 Valparaíso, Chile.
Ana Maria Vega-LetterEscuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, 2340000 Valparaíso, Chile; Center for Interdisciplinary Research in Biomedicine, Biotechnology and Well-Being (CID3B), Pontificia Universidad Católica de Valparaíso, 2340000 Valparaíso, Chile.
Bradley PriemDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Haoyu Chris CaoDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Martin HoldDepartment of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria.
Junyu MaDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Yi Fan HongBioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Republic of Singapore.
Saratram GopalakrishnanDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 92093, USA; Center for Molecular Medicine, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Blaise Manga EnuhGreat Lakes Bioenergy Research Centre (GLBRC), Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI 53707, USA.
Chaimaa TarziSchool of Computing, Engineering and Digital Technologies, Teesside University, Middlesbrough TS1 3BX, UK.
Kuin Tian PangBioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Republic of Singapore; Bioinformatics Institute, Agency for Science, Technology and Research (A(∗)STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Republic of Singapore; Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3 Block 4, #04-08, Singapore 117583, Republic of Singapore; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 62 Nanyang Drive, N1.2-B3, Singapore 637459, Republic of Singapore.
Claudio AngioneSchool of Computing, Engineering and Digital Technologies, Teesside University, Middlesbrough TS1 3BX, UK; Centre for Digital Innovation, Teesside University, Middlesbrough TS1 3BX, UK; National Horizons Centre, Darlington DL1 1HG, UK.
Jürgen ZanghelliniDepartment of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria.
Cleo KontoravdiDepartment of Chemical Engineering, Imperial College London, London SW7 2AZ, UK.
Hooman HefziDepartment of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Lyngby, Denmark.
Michael J BetenbaughDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Lars K NielsenNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark; Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
Meiyappan LakshmananDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India; Centre for Integrative Biology and Systems medicinE (IBSE), Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Republic of Singapore; Wadhwani School of Data Science and AI (WSAI), Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India. Electronic address: meiyappan@iitm.ac.in.
Dong-Yup LeeSchool of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: dongyuplee@skku.edu.
Anne RichelleSartorius Corporate Research, 1180 Brussels, Belgium. Electronic address: anne.richelle@sartorius.com.
Nathan E LewisDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 92093, USA; Center for Molecular Medicine, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA. Electronic address: natelewis@uga.edu.
Funding
Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3MNIGMS NIH HHS R35 GM119850
Abstract
Genome-scale metabolic models (GEMs) are indispensable for studying cellular metabolism. We present iCHO3K, a community-consensus, manually curated reconstruction of the Chinese hamster metabolic network. Spanning 11,004 reactions linked to 3,597 genes, iCHO3K augments the network with 3,489 protein structures and physicochemical descriptors for >70% of 7,377 metabolites, enabling structure-aware analyses. We applied iCHO3K to contextualize transcriptomics and metabolomics from a fed-batch Chinese hamster ovary (CHO) cell line engineered to abolish lactate secretion. The model indicated reduced glycolytic flux with enhanced tricarboxylic acid (TCA) activity and elevated intracellular NADH and phosphoenolpyruvate (PEP), consistent with experimental measurements. Leveraging iCHO3K's structural annotations, we evaluated potential off-target binding of NADH and PEP across early glycolytic enzymes and identified a putative allosteric PEP interaction with phosphofructokinase, suggesting a structural mechanism underlying reduced glucose uptake and glycolytic flux. Overall, iCHO3K provides a framework for systematic multi-omics integration, improved flux prediction, and structure-guided mechanistic insight, advancing CHO cell engineering and biomanufacturing. A record of this paper's transparent peer review process is included in the supplemental information.
Indexed as
Systems BiologyAnimalsCHO CellsCricetinaeCricetulusGlycolysisLactic AcidMetabolic Networks and PathwaysMetabolomicsNADLactic AcidNADChinese hamsterCHO bioprocessingenzyme-constrained flux balance analysisgenome-scale metabolic modeliCHO3Kstructural systems biologyWarburg effect
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