Amalgamation of nucleosides and amino acids in antibiotic biosynthesis: Discovery of an l -threonine: Uridine-5′-aldehyde transaldolase

Sandra Barnard-Britson, Xiuling Chi, Koichi Nonaka, Anatol P. Spork, Nidhi Tibrewal, Anwesha Goswami, Pallab Pahari, Christian Ducho, Jurgen Rohr, Steven G. Van Lanen

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)18514-18517
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number45
DOIs
StatePublished - Nov 14 2012

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

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