Metabolic selection of glycosylation defects in human cells

Kevin J Yarema, Scarlett Goon, Carolyn R. Bertozzi

Research output: Contribution to journalArticle

Abstract

Changes in glycosylation are often associated with disease progression, but the genetic and metabolic basis of these events is rarely understood in detail at a molecular level. We describe a metabolism-based approach to the selection of mutants in glycoconjugate biosynthesis that provides insight into regulatory mechanisms for oligosaccharide expression and metabolic flux. Unnatural intermediates are used to challenge a specific pathway, and cell surface expression of their metabolic products provides a readout of flux in that pathway and a basis for selecting genetic mutants. The approach was applied to the sialic acid metabolic pathway in human cells, yielding novel mutants with phenotypes related to the inborn metabolic defect sialuria and metastatic tumor cells.

Original languageEnglish (US)
Pages (from-to)553-558
Number of pages6
JournalNature Biotechnology
Volume19
Issue number6
DOIs
StatePublished - 2001

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ASJC Scopus subject areas

  • Microbiology

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