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Systematic discovery of analogous enzymes in thiamin biosynthesis

Item Type:Article
Title:Systematic discovery of analogous enzymes in thiamin biosynthesis
Creators Name:Morett, E. and Korbel, J. and Rajan, E. and Saab-Rincon, G. and Olvera, L. and Olvera, M. and Steffen, S. and Snel, B. and Bork, P.
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.
Keywords:Alkyl and Aryl Transferases, Amino Acid Sequence, Amino Acid Sequence Homology, Biological Models, Energy Metabolism, Escherichia Coli, Isoenzymes, Molecular Sequence Data, Protein Sequence Analysis, Sequence Alignment, Species Specificity, Thiamine, Animals
Source:Nature Biotechnology
Publisher:Nature Publishing Group
Page Range:790-795
Date:July 2003
Official Publication:https://doi.org/10.1038/nbt834
PubMed:View item in PubMed

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