Translational errors during recombinant protein synthesis.

Cloned human genes can now be readily expressed in organisms like Escherichia coli (E. coli) and fungi and this has made recombinant human proteins available for use in clinical medicine. Expressing foreign proteins at high rates to make them major cell components can, however, lead to nutritional stresses in the production cells. Such stresses markedly increase the frequency of random translational errors, both in model laboratory experiments and in actual fermentations. The burden of detecting and removing errors then falls on the purification processes. Random errors are, however, difficult to detect as they will produce a heterogeneous mixture of polypeptides. Each type of altered protein may be present in quite small amounts but the total number of erroneous molecules could be substantial. Little is known about how erroneous proteins could affect patients and much more information is needed to clarify this problem. Techniques for limiting and monitoring translational errors are briefly discussed.