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