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 A. Gerlt

Research output: Contribution to journalArticle


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
Issue number46
StatePublished - Nov 25 2015


ASJC Scopus subject areas

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

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