Methylthioadenosine (MTA) Boosts Cell-specific Productivities of Chinese Hamster Ovary Cultures: Dosage Effects on Proliferation, Cell Cycle and Gene Expression

A major goal for process and cell engineering in the biopharmaceutical industry is enhancing production through increasing volumetric and cell-specific productivities (CSP). Here, we present 5'-deoxy-5'-(methylthio)adenosine (MTA), the degradation product of S-(5'-adenosyl)-L-methionine (SAM), as a highly attractive native additive which can boost CSP by 79% when added to exponentially growing cells at a concentration of 250-300 μm. Notably, cell viability and cell size remain higher than in non-treated cultures. In addition, cell cycle arrests first in S-, then in G2-phase before levelling out compared to non-treated cultivations. Intensive differential gene analysis reveals that expression of genes for cytoskeleton mediated proteins and vesicle transport is amplified by treatment. Furthermore, the interaction of MTA with cell proliferation additionally stimulated recombinant protein formation. The results may serve as a promising starting point for further developments in process and cell engineering to boost productivity.