Glutamine substitution: the role it can play to enhance therapeutic protein production

The biopharmaceutical market is driven by the steady increase in demand for therapeutic proteins produced in mammalian cells. Glutamine is a main nitrogen source and also a main energy source with glucose in mammalian cell cultures for therapeutic protein production. As a result of glutamine metabolism and the natural decomposition of glutamine, ammonia, which is known to negatively affect cell growth, protein production and sialylation of recombinant glycoprotein, is necessarily accumulated in a culture medium. This review highlights the current strategies and achievements in overcoming the negative effect of ammonia through the glutamine substitution by less ammoniagenic substrates, such as glutamate, pyruvate and α-ketoglutarate.