The vesicle-trafficking protein munc18b increases the secretory capacity of mammalian cells.
Heterologous protein production in mammalian cells is often challenged by the bottleneck of the secretory machinery, which prevents producer cells from fully exploiting their physiologic capacity in the production of biopharmaceuticals. Recent advances in the understanding of the molecular mechanisms of vesicle trafficking have enabled the identification of key regulators that control the flow of recombinant proteins along the secretory pathway. Here, we report that transgenic expression of Munc18b, a Sec1/Munc18 (SM) protein regulating the fusion of secretory vesicles to the plasma membrane, enhances the secretory capacity of HeLa, HEK-293 and HT-1080 and so increases overall production of different secreted human glycoproteins as well as the titer of lentiviral particles produced in HEK-293-derived helper cells. Targeted interventions in secretory vesicle trafficking by Munc18b is a novel secretion engineering strategy, which harnesses the full secretory capacity of mammalian cells. Secretion engineering is the latest-generation metabolic engineering strategy, which could improve future therapies by increasing the production of biopharmaceuticals by boosting the secretion performance of cell implants in cell therapy initiatives and by raising the production titers of transgenic viral particles used for gene therapy applications.
Peng
Ren-Wang
RW
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Guetg
Claudio
C
Tigges
Marcel
M
Fussenegger
Martin
M
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051938:Munc18 Proteins / Q000096:biosynthesis* / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism*
D051938:Munc18 Proteins; D011994:Recombinant Proteins