|
type |
Journal Article |
authors |
Barnard-Britson, S,; Chi, X.; Nonaka, K.; Spork, A.P.; Tibrewal, N.; Goswami, A.; Pahari, P.; Ducho, C.; Rohr, J.; Van Lanen, S.G. |
title |
Amalgamation of Nucleosides and Amino Acids in Antibiotic Biosynthesis: Discovery of an L-Threonine:Uridine-5'-Aldehyde Transaldolase |
journal |
J Am Chem Soc |
Activity |
lipk |
Family |
lipk |
sel |
selected |
ui |
23110675 |
year |
(2012) |
volume |
134 |
number |
45 |
pages |
18514-7 |
| |
abstract |
The lipopeptidyl nucleoside antibiotics represented by A-90289, caprazamycin, and muraymycin are structurally highlighted by a nucleoside core that contains a nonproteinogenic β-hydroxy-α-amino acid named 5'-C-glycyluridine (GlyU). Bioinformatic analysis of the biosynthetic gene clusters revealed a shared open reading frame encoding a protein with sequence similarity to serine hydroxymethyltransferases, resulting in the proposal that this shared enzyme catalyzes an aldol-type condensation with glycine and uridine-5'-aldehyde to furnish GlyU. Using LipK involved in A-90289 biosynthesis as a model, we now functionally assign and characterize the enzyme responsible for the C-C bond-forming event during GlyU biosynthesis as an l-threonine:uridine-5'-aldehyde transaldolase. Biochemical analysis revealed this transformation is dependent upon pyridoxal-5'-phosphate, the enzyme has no activity with alternative amino acids, such as glycine or serine, as aldol donors, and acetaldehyde is a coproduct. Structural characterization of the enzyme product is consistent with stereochemical assignment as the threo diastereomer (5'S,6'S)-GlyU. Thus this enzyme orchestrates C-C bond breaking and formation with concomitant installation of two stereocenters to make a new l-α-amino acid with a nucleoside side chain. |
last changed |
2016/10/05 15:13 |
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