Abstract
Muraminomicin is a lipopeptidyl nucleoside antibiotic produced by Streptosporangium amethystogenes SANK 60709. Similar to several members of this antibiotic family such as A-90289 and muraymycin, the structure of muraminomicin consists of a disaccharide comprised of two modified ribofuranose units linked by an O-β(1 → 5) glycosidic bond; however, muraminomicin holds the distinction in that both ribose units are 2-deoxy sugars. The biosynthetic gene cluster of muraminomicin has been identified, cloned and sequenced, and bioinformatic analysis revealed a minimum of 24 open reading frames putatively involved in the biosynthesis, resistance, and regulation of muraminomicin. Fives enzymes are likely involved in the assembly and attachment of the 2,5-dideoxy-5-aminoribose saccharide unit, and two are now functionally assigned and characterized: Mra20, a 5'-amino-2',5'-dideoxyuridine phosphorylase and Mra23, a UTP:5-amino-2,5-dideoxy-α-D-ribose-1-phosphate uridylyltransferase. The cumulative results are consistent with the incorporation of the ribosyl appendage of muraminomicin via the archetypical sugar biosynthetic pathway that parallels A-90289 biosynthesis, and the specificity for this appendage is dictated primarily by the two characterized enzymes.