Systematic discovery of analogous enzymes in thiamin biosynthesis

Enrique Morett, Jan O. Korbel, Emmanuvel Rajan, Gloria Saab-Rincon, Leticia Olvera, Maricela Olvera, Steffen Schmidt, Berend Snel, Peer Bork

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In all genome-sequencing projects completed to date, a considerable number of 'gaps' have been found in the biochemical pathways of the respective species. In many instances, missing enzymes are displaced by analogs, functionally equivalent proteins that have evolved independently and lack sequence and structural similarity. Here we fill such gaps by analyzing anticorrelating occurrences of genes across species. Our approach, applied to the thiamin biosynthesis pathway comprising approximately 15 catalytic steps, predicts seven instances in which known enzymes have been displaced by analogous proteins. So far we have verified four predictions by genetic complementation, including three proteins for which there was no previous experimental evidence of a role in the thiamin biosynthesis pathway. For one hypothetical protein, biochemical characterization confirmed the predicted thiamin phosphate synthase (ThiE) activity. The results demonstrate the ability of our computational approach to predict specific functions without taking into account sequence similarity.
Original languageEnglish
Pages (from-to)790-795
Number of pages6
JournalNature Biotechnology
Volume21
Issue number7
DOIs
Publication statusPublished - 1 Jul 2003

Keywords

  • enzyme
  • synthetase
  • thiamine
  • thiamine phosphate synthase
  • unclassified drug
  • article
  • enzyme activity
  • enzyme synthesis
  • gene
  • gene sequence
  • genetic complementation
  • genome
  • nonhuman
  • priority journal
  • structure analysis
  • thiamine biosynthesis

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