title: Biosynthetic origin and mechanism of formation of the aminoribosyl moiety of peptidyl nucleoside antibiotics.
abstract: Several peptidyl nucleoside antibiotics that inhibit bacterial translocase I involved in peptidoglycan cell wall biosynthesis contain an aminoribosyl moiety, an unusual sugar appendage in natural products. We present here the delineation of the biosynthetic pathway for this moiety upon in vitro characterization of four enzymes (LipM-P) that are functionally assigned as (i) LipO, an L-methionine:uridine-5'-aldehyde aminotransferase; (ii) LipP, a 5'-amino-5'-deoxyuridine phosphorylase; (iii) LipM, a UTP:5-amino-5-deoxy-α-D-ribose-1-phosphate uridylyltransferase; and (iv) LipN, a 5-amino-5-deoxyribosyltransferase. The cumulative results reveal a unique ribosylation pathway that is highlighted by, among other features, uridine-5'-monophosphate as the source of the sugar, a phosphorylase strategy to generate a sugar-1-phosphate, and a primary amine-requiring nucleotidylyltransferase that generates the NDP-sugar donor.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536, USA.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Chi
authors.forename: Pallab
authors.initials: P
authors.lastname: Pahari
authors.forename: Koichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Steven G
authors.initials: SG
authors.lastname: Van Lanen
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D006031:Glycosylation; D009705:Nucleosides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000737:chemistry*; D010430:Pentosyltransferases / Q000737:chemistry*; D000637:Transaminases / Q000737:chemistry*; D014543:Uridine Phosphorylase
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D009705:Nucleosides; D010430:Pentosyltransferases; D014543:Uridine Phosphorylase; C035146:deoxyuridine phosphorylase; D000637:Transaminases; D009713:Nucleotidyltransferases