Synthetic biology has shown highly promising results in tackling real-world problems in medicine and bioprocessing. The ability to use biological tools from many different sources enabled engineers to develop intricate cellular systems. First smart cell-based and gene therapies are currently being applied in the clinic and the production of therapeutic antibodies using metabolically engineered cells is well established. To advance the development of engineered medical and biopharmaceutical systems, it is an essential task to establish the heterologous gene expression in mammalian cells and to develop conceptually novel tools for bioengineering. In this thesis we present the design of two new tools based on the metabolic engineering of a heterologous small molecule biosynthesis- and a utilizationpathway. In chapter I we introduce a reporter system for mammalian cells, based on the expression of a combination of two human genes together with one gene from Amanita muscaria. Expressing all three genes resulted in the formation of a yellow, fluorescent dye derived from the metabolic amino acid L-tyrosine. The dye belongs to the betaxanthin class, it can be detected extra- and intracellularly and its production does not seem to impact cell viability. This offers multiple approaches for quantification, in particular plate readers, flow cytometry and microscopy. Additionally, we show how the system can be used as a reporter for gene expression in mammalian cells with comparable performance as standardized reporter systems. In chapter II we show the approach to endow CHO-K1 cells with the ability to metabolize the disaccharide cellobiose using a cellobiose specific transporter and a β-glucosidase. This metabolic engineering approach enables cells to survive in cellobiose medium without glucose, whereas untransfected cells quickly died. This cellobiose utilization pathway was used to create the additive stable cell line selection method called CelloSelect. A detailed selection protocol was established to create long-term stable cells in a matter of days. We show that these stable cells can be grown in cellobiose- or glucose-culture medium and that the cells continue to express the cargo protein at the same expression level for the tested period of 30 days independent of medium composition. In a proof-of-concept bioprocessing experiment we conclude that the system can be used to produce a therapeutic protein.