Metabolomics and mass spectrometry imaging reveal channeled de novo purine synthesis in cells

Vidhi Pareek, Hua Tian, Nicholas Winograd, Stephen J. Benkovic

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Metabolons, multiprotein complexes consisting of sequential enzymes of a metabolic pathway, are proposed to be biosynthetic "hotspots" within the cell. However, experimental demonstration of their presence and functions has remained challenging. We used metabolomics and in situ three-dimensional submicrometer chemical imaging of single cells by gas cluster ion beam secondary ion mass spectrometry (GCIB-SIMS) to directly visualize de novo purine biosynthesis by a multienzyme complex, the purinosome. We found that purinosomes comprise nine enzymes that act synergistically, channeling the pathway intermediates to synthesize purine nucleotides, increasing the pathway flux, and influencing the adenosine monophosphate/guanosine monophosphate ratio. Our work also highlights the application of high-resolution GCIB-SIMS for multiplexed biomolecular analysis at the level of single cells.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalScience
Volume368
Issue number6488
DOIs
StatePublished - Apr 17 2020

All Science Journal Classification (ASJC) codes

  • General

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