Activities | Families | Sequences | Fold types | References | Help
B6db references: 23110675

type Journal Article
authors Sandra Barnard-Britson, Xiuling Chi, Koichi Nonaka, Anatol P. Spork, Nidhi Tibrewal, Anwesha Goswami, Pallab Pahari, Christian Ducho, Jurgen Rohr, and Steven G. Van Lanen.
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
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 2014/02/21 14:32

B6db references