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Abstract
Cobamides are organo-metallic tetrapyrroles that are required for all domains in life, These marco-cyclic compounds are an essential component in cellular function. Cobamides are essential to all domains of life. Notably, cobamides are only synthesized de novo by some bacteria and archaea. The complexity of the chemical structure of cobamides has challenged chemists, biologists, and biophysicists alike for many decades. In spite of these efforts, our understanding of how this macrocyclic molecule is assembled, remains incomplete. The functions of the enzymes CbiZ (cobyric acid-forming amidohydrolase) and CbiB (cobinamide-phosphate synthase) remain unknown. In most archaea and some bacteria CbiZ functions as a remodeling systems of corrinoids. CbiZ cleaves corrinoids at the amide bond of the amino-propanol moiety, this reaction yields cobyric acid which can re-enter B12 biosynthesis pathway and acts as a co-substrate of CbiB. The foci of this work uses Salmonella enterica serovar Typhimurium LT2 to dissect the activity of the enzymes and the connections of CbiZ to CbiB.