|
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.
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last changed |
2018/11/27 08:53 |
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