A General Strategy for the Discovery of Metabolic Pathways

D -Threitol, l -Threitol, and Erythritol Utilization in Mycobacterium smegmatis

Hua Huang, Michael S. Carter, Matthew W. Vetting, Nawar Al-Obaidi, Yury Patskovsky, Steven C. Almo, John Alan Gerlt

Research output: Contribution to journalArticle

Abstract

We describe a general integrated bioinformatic and experimental strategy to discover the in vitro enzymatic activities and in vivo functions (metabolic pathways) of uncharacterized enzymes discovered in microbial genome projects using the ligand specificities of the solute binding proteins (SBPs) for ABC transporters. Using differential scanning fluorimetry, we determined that the SBP for an ABC transporter encoded by the genome of Mycobacterium smegmatis is stabilized by d-threitol. Using sequence similarity networks and genome neighborhood networks to guide selection of target proteins for pathway enzymes, we applied both in vitro and in vivo experimental approaches to discover novel pathways for catabolism of d-threitol, l-threitol, and erythritol.

Original languageEnglish (US)
Pages (from-to)14570-14573
Number of pages4
JournalJournal of the American Chemical Society
Volume137
Issue number46
DOIs
StatePublished - Nov 25 2015

Fingerprint

Erythritol
Mycobacterium smegmatis
Metabolic Networks and Pathways
ATP-Binding Cassette Transporters
genome
Genes
protein
solute
Carrier Proteins
Enzymes
Microbial Genome
Genome
enzyme
fluorometry
Fluorometry
bioinformatics
catabolism
Bioinformatics
Computational Biology
ligand

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

A General Strategy for the Discovery of Metabolic Pathways : D -Threitol, l -Threitol, and Erythritol Utilization in Mycobacterium smegmatis. / Huang, Hua; Carter, Michael S.; Vetting, Matthew W.; Al-Obaidi, Nawar; Patskovsky, Yury; Almo, Steven C.; Gerlt, John Alan.

In: Journal of the American Chemical Society, Vol. 137, No. 46, 25.11.2015, p. 14570-14573.

Research output: Contribution to journalArticle

Huang, Hua ; Carter, Michael S. ; Vetting, Matthew W. ; Al-Obaidi, Nawar ; Patskovsky, Yury ; Almo, Steven C. ; Gerlt, John Alan. / A General Strategy for the Discovery of Metabolic Pathways : D -Threitol, l -Threitol, and Erythritol Utilization in Mycobacterium smegmatis. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 46. pp. 14570-14573.
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