Encodes a Unique Mannosyl-1-Phosphotransferase for Polysaccharide II Biosynthesis.

() is the leading cause of antibiotic-induced bacterial colitis and life-threatening diarrhea worldwide. The commonly existing anionic polysaccharide II (PSII) is responsible for protein anchoring involved in colonization, and the gene located in its biosynthesis gene cluster is essential for bacterial growth. Herein, we demonstrated that encodes a novel mannosyl-1-phosphotransferase (ManPT) responsible for the phosphorylation of PSII. Unlike typical mannosyltransferases, CD2775 transfers mannose-α1-phosphate instead of mannose from guanosine 5'-diphospho-d-mannose to disaccharide acceptors, forming a unique mannose-α1-phosphate-6-glucose linkage. The enzyme was overexpressed in and purified for biochemical characterization and substrate specificity study. It is found that CD2775 possesses a strict acceptor specificity toward Glc-β1,3-GalNAc-diphospho-lipids but extreme promiscuity toward various sugar donors. This is the first report of a ManPT in all living systems. Given its essentiality in growth, CD2775 can be a promising target for therapeutics development.