J. Antibiot. 60(8): 485–491, 2007

Tunicamycins are nucleotide sugar analogs produced by several Streptomyces species. In eukaryotes, tunicamycins inhibit UDP-N-acetylglucosamine: dolichol phosphate GlcNAc-1-P transferase (GPT) that catalyzes the first step in protein glycosylation. In bacteria they inhibit UDP-N-acetylmuramoyl-pentapeptide: undecaprenol phosphate MurNAc-pentapeptide-1-P transtransferase (MraY) that catalyzes an early stage in peptidoglycan cell wall assembly. Tunicamycins are substrate analog of GPT and MraY, such that the ab -1 ,11 -linked GlcNAc residue of the tunicamycins mimics the transferred GlcNAc1-phosphate. The unusual structure of tunicamycins, particularly the unique 11-carbon sugar, tunicamine, and the ab -1 ,11 -O-glycosidic linkage, suggest its biosynthesis to be unique. This review discusses potential biosyntheses for tunicamycins via the synthesis and conjugation of uridine-5 -aldehyde and UDP-4-keto-Nacetylgalactosamine-5,6-ene and the subsequent formation of the a ,b-1 ,11 glycosidic linkage.