Significance Penicillin-binding proteins (PBPs) synthesize the bacterial cell wall. These enzymes are important therapeutic targets, but little is known about how their activity is controlled to promote proper cell morphogenesis. Uncovering these regulatory mechanisms promises to reveal new approaches for disrupting cell wall biogenesis for antibiotic development. Here, we identify MacP as a factor required for PBP activity in the pathogen Streptococcus pneumoniae . We further show that MacP is a substrate of the kinase and global cell cycle regulator StkP and that phosphorylation is required for PBP activation by MacP. Our results support a model in which StkP and MacP form part of the regulatory network that coordinates cell wall synthesis with other morphogenetic activities during the cell cycle.