PXD041650

PXD041650 is an original dataset announced via ProteomeXchange.

Title	Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches
Description	Optimizing the production of recombinant proteins is a problem of major industrial and pharmaceutical importance. Secretion of the protein by the host cell considerably simplifies downstream purification processes. However, for many proteins, this is also the limiting production step. Current solutions involve extensive engineering of the chassis cell to facilitate protein trafficking and limit protein degradation triggered by excessive secretion-associated stress. Here, we propose instead a regulation-based strategy in which induction is dynamically adjusted to an optimal strength based on the current stress level of the cells. Using a small collection of hard-to-secrete proteins, a bioreactor-based platform with automated cytometry measurements, and a systematic assay to quantify secreted protein levels, we demonstrate that the secretion sweet spot is indicated by the appearance of a subpopulation of cells that accumulate high amounts of proteins, decrease growth, and face significant stress, that is, experience a secretion burnout. In these cells, adaptations capabilities are overwhelmed by a too strong production. Using these notions, we show for a single-chain antibody variable fragment that secretion levels can be improved by 70% by dynamically keeping the cell population at optimal stress levels using real-time closed-loop control.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:51:32.421.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MARIETTE MATONDO
SpeciesList	scientific name: Saccharomyces cerevisiae; NCBI TaxID: NCBITaxon:4932; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-19 07:08:32	ID requested
1	2023-06-30 06:04:56	announced
2	2024-10-03 04:19:10	announced	2024-10-03: Updated project metadata.
⏵ 3	2024-10-22 05:51:33	announced	2024-10-22: Updated project metadata.

10.1038/s41467-023-38807-9;

Sosa-Carrillo S, Galez H, Napolitano S, Bertaux F, Batt G, Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches. Nat Commun, 14(1):3028(2023) [pubmed]

submitter keyword: protein quantification, secretory

Gregory Batt
contact affiliation	Institut Pasteur, Inria, Université Paris Cité, 75015 Paris, France
contact email	gregory.batt@inria.fr
lab head
MARIETTE MATONDO
contact affiliation	Pasteur
contact email	mariette.matondo@pasteur.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD041650

PRIDE project URI

• PRIDE
  1. PXD041650
     1. Label: PRIDE project
     2. Name: Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches