The biosynthesis of caprazamycins and related liponucleoside antibiotics: new insights.

The first step in the membrane cycle of reactions during peptidoglycan biosynthesis is the transfer of phospho-MurNAc-pentapeptide from UDP-MurNAc-pentapeptide to undecaprenyl phosphate, catalyzed by the integral membrane protein MraY translocase. Different MraY inhibitors are known and can be subdivided into classes depending on their structural composition. Caprazamycins belong to the liponucleoside class of antibiotics isolated from Streptomyces sp. MK730-62F2. They possess activity in vitro against Gram-positive bacteria, in particular against the genus Mycobacterium including Mycobacterium intracellulare, Mycobacterium avium and Mycobacterium tuberculosis. Caprazamycins and the structurally related liposidomycins and A-90289 share a unique composition of moieties. Their complex structure is derived from 5'-(β-O-aminoribosyl)-glycyluridine and comprises a unique N,N'-dimethyldiazepanone ring. Recently, the corresponding biosynthetic gene clusters of caprazamycins, liposidomycins and A-90289 have been discovered and will be compared in this review. New information is also emerging regarding the biosynthesis of liponucleoside antibiotics obtained by gene disruption experiments and biochemical investigations.