Streptococcus pneumoniae is an important respiratory pathogen that causes more than two million deaths worldwide annually. Similar to many pathogenic bacteria, S. pneumoniae encases its cell envelope with capsular polysaccharide (CPS), which protects it from opsonophagocytosis and mucus clearance. Because of its importance in pathogenesis, all clinically relevant vaccines against S. pneumoniae target the CPS. There are over 90 serotypes identified in S. pneumoniae. The structural variance in CPS produced is attributed to the extreme diversity of enzymes located in the cps locus. Although these enzymes were identified decades ago, little is known about the molecular mechanisms governing their specificity, regulation, and function. Therefore, the long-term goal of our research program is to address this knowledge gap by investigating how specificity is determined for CPS enzymes.