An improved system for large scale production of polypeptides in cell culture is provided. In accordance with the present invention, cells expressing a polypeptide of interest are grown in media that contain copper, glutamate or both. The use of such a system allows production of polypeptides in which misfolding and/or aggregation are reduced, and in which total glycosylation is increased. Polypeptides expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical, agricultural or other commercial compositions.