Systems biology and metabolic modeling for cultivated meat: A promising approach for cell culture media optimization and cost reduction

Abstract

The cultivated meat industry, also known as cell-based meat, cultured meat, lab-grown meat, or meat alternatives, is a growing field that aims to generate animal tissues ex-vivo in a cost-effective manner that achieves price parity with traditional agricultural products. However, cell culture media costs account for 55%-90% of production costs. To address this issue, efforts are aimed at optimizing media composition. Systems biology-driven approaches have been successfully used to improve the biomass and productivity of multiple bioproduction platforms, like Chinese hamster ovary cells, by accelerating the development of cell line-specific media and reducing research and development and production costs related to cell media and its optimization. In this review, we summarize systems biology modeling approaches, methods for cell culture media and bioprocess optimization, and metabolic studies done in animals of interest to the cultivated meat industry. More importantly, we identify current gaps in knowledge that prevent the identification of metabolic bottlenecks. These include the lack of genome-scale metabolic models for some species (pigs and ducks), a lack of accurate biomass composition studies for different growth conditions, and ¹³ C-metabolic flux analysis (MFA) studies for many of the species of interest for the cultivated meat industry (only shrimp and duck cells have been subjected to ¹³ C-MFA). We also highlight the importance of characterizing the metabolic requirements of cells at the organism, breed, and cell line-specific levels, and we outline future steps that this nascent field needs to take to achieve price parity and production efficiency similar to those of other bioproduction platforms. Practical Application: Our article summarizes systems biology techniques for cell culture media design and bioprocess optimization, which may be used to significantly reduce cell-based meat production costs. We also present the results of experimental studies done on some of the species of interest to the cultivated meat industry and highlight why modeling approaches are required for multiple species, cell-types, and cell lines.

Keywords: biotechnology; cultivated meat; fermentation; mathematical modeling; meat science; metabolism.