Direct Amide Bond Formation By A Spore Peptidoglycan Biosynthetic Enzyme

The cortex layer of the peptidoglycan cell wall surrounding bacterial spores contains a modified sugar, muramic-δ-lactam, that is essential for spore germination. Genetic evidence has linked the conserved enzyme SwsB to the muramic-δ-lactam biosynthetic pathway. SwsB belongs to a large family of metal-dependent deacetylases, but its function is unclear because a putative catalytic residue is mutated. We have used native cortex peptidoglycan substrates to show that SwsB acts not as a deacetylase but as a monofunctional muramic-δ-lactam cyclase, the first enzyme reported with this activity. SwsB is remarkable in that it catalyzes lactam synthesis by direct intramolecular condensation of a carboxylate and primary amine with no apparent requirement for chemical energy input. SwsB will accept a minimal peptidoglycan substrate and, surprisingly, does not require a metal ion cofactor for cyclase activity. Our results suggest anin vivorole for SwsB and lay the foundation for mechanistic and structural studies of an unusual enzyme.