Activities | Families | Sequences | Fold types | References | Help
B6db references: 29768920

type Journal Article
authors Cui Z, Liu X, Overbay J, Cai W, Wang X, Lemke A, Wiegmann D, Niro G, Thorson JS, Ducho C, Van Lanen SG
title Enzymatic Synthesis of the Ribosylated Glycyl-Uridine Disaccharide Core of Peptidyl Nucleoside Antibiotics
journal J Org Chem
Activity lipo
Family lipo
sel selected
ui 29768920
year (2018)
volume 83
number 13
pages 7239-7249
keywords doi: 10.1021/acs.joc.8b00855
abstract Muraymycins belong to a family of nucleoside antibiotics that have a distinctive disaccharide core consisting of 5-amino-5-deoxyribofuranose (ADR) attached to 6'-N-alkyl-5'- C-glycyluridine (GlyU). Here we functionally assign and characterize six enzymes from the muraymycin biosynthetic pathway involved in the core assembly that starts from UMP. The biosynthesis is initiated by Mur16, a non-heme Fe(II)- and α- ketoglutarate- dependent dioxygenase, followed by four transferase enzymes-Mur17, a pyridoxal-5'-phosphate (PLP)-dependent transaldolase; Mur20, an aminotransferase; Mur26, a pyrimidine phosphorylase; and Mur18, a nucleotidylyltransferase. The pathway culminates in glycosidic bond formation in a reaction catalyzed by an additional transferase enzyme, Mur19, a ribosyltransferase. Analysis of the biochemical properties revealed several noteworthy discoveries including that (i) Mur16 and downstream enzymes can also process 2'-deoxy-UMP to generate a 2-deoxy-ADR, which is consistent with the structure of some muraymycin congeners; (ii) Mur20 prefers L-Tyr as the amino donor source; (iii) Mur18 activity absolutely depends on the amine functionality of the ADR precursor, consistent with the nucleotidyltransfer reaction occurring after the Mur20-catalyzed aminotransfer reaction; and (iv) the bona fide sugar acceptor for Mur19 is (5' S,6' S)-GlyU, suggesting that ribosyltransfer occurs prior to N- alkylation of GlyU. Finally, a one-pot, six-enzyme reaction was utilized to generate the ADR-GlyU disaccharide core starting from UMP.
last changed 2018/11/27 08:53

B6db references