Collagen binding domain fusion proteins are of significant importance because of their potential as therapeutic biomaterials. In this paper, we investigate the production of such therapeutic proteins via fermentation of Escherichia coli on both an undefined medium and a defined medium. Defined media with amino acid supplementation provided higher amounts of therapeutic protein than undefined media with no supplementation. Additionally, utilizing lactose instead of isopropyl--d-thio-galactoside (IPTG) for induction and extending batch time yielded higher amounts of the model therapeutic. (c) 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:503-509, 2015