In 1993, the World Heath Organization declared tuberculosis (TB) a “global health emergency.” TB, which results from infection with the tubercle bacillus M. tuberculosis, now infects one-third of the world’s population and kills two million people annually. The increase in the death toll is largely due to the emergence of antibiotic-resistant strains, indicating the need for new treatments. The complex cell wall of TB acts as a formidable barrier against cellular destruction and is essential to the viability of the organism. To address this growing health threat, an understanding of the enzymes that mediate bacterial cell wall biosynthesis is essential. One of the enzymes that contributes to the cell wall, uridine 5'-diphosphate (UDP)-galactopyranose mutase (UGM), is responsible for the isomerization of the thermodynamically favored UDP-galactopyranose (UDP-Galp) to the disfavored UDP-galactofuranose (UDP-Galf). UGM is a critical participant in cell wall construction of many bacteria, protozoa, and fungi and is necessary for mycobacterial growth. Although the catalytic mechanism of the sugar isomerization is controversial, it is known that enzymatic activity is dependent on a fully reduced flavin adenine dinucleotide cofactor (FAD). We propose that FAD is directly involved in catalysis and that instead of performing a redox or structural role, the reduced flavin acts as a nucleophile. Recently, we obtained compelling biochemical data in support of this proposal. We plan to monitor enzymatic activity in the presence of several FAD analogs. Synthetic routes to both 1-deaza and 5-deazariboflavin are known; however, both have proven to be difficult to carry out and irreproducible. Thus, new synthetic pathways to both riboflavin analogs were designed and executed. Design and application of a high-throughput screen for UGM resulted in the identification of several low micromolar inhibitors of UGM from K. pneumoniae and M. tuberculosis. The design and synthesis of a directed library of compounds, based on the structure of the most potent inhibitor, is currently under investigation.