Proteome constrained metabolic modeling of Sus scrofa muscle stem cells for cultured meat production

Cultured meat has recently emerged as a sustainable alternative to the traditional livestock farming and gained attention as a promising future protein source. Herein, the Sus scrofa muscle stem cell is a commonly used cell source in the cell proliferation step of cultured meat production. However, a major bottleneck of large-scale cultivation is the inhibition by secreted and accumulated lactate and ammonium in the process of S. scrofa cell proliferation. To simulate the growth and metabolism of S. scrofa muscle stem cells under different lactate and ammonium concentrations, this study constructed the first proteome constrained metabolic model for the core metabolism of S. scrofa muscle stem cells, pcPigGEM2025. The relationship of lactate and ammonium levels with cellular metabolism was derived from growth and metabolomics data of two culture conditions with low and high initial ammonium concentrations, and then incorporated into metabolic flux simulation. Metabolic flux simulations for experimental conditions, along with perturbation simulations considering stressed non-growth associated maintenance and oxygen supply, demonstrated that pcPigGEM2025 could effectively characterize the response of the S. scrofa muscle stem cells growth and metabolism to varying environmental conditions, shedding light on model-aided control and optimization of the cultured meat production process. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/679571v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@a4526aorg.highwire.dtl.DTLVardef@1ee2d1org.highwire.dtl.DTLVardef@1bd4700org.highwire.dtl.DTLVardef@18079e6_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe first proteome constrained metabolic model was built for S. scrofa myoblasts. C_LIO_LIThis model effectively simulated myoblast metabolism under lactate and NH4+ stress. C_LIO_LIPerturbation simulations showed that this model could also account for other stress. C_LIO_LIThis model enables in-silico control and optimization of cultured meat production. C_LI