Puzzling over orphan enzymes.

Despite the current availability of several hundreds of thousands of amino acid sequences, more than 39% of the well-defined enzyme activities (EC numbers) are not associated with any sequence in major public databases. This wide gap separating knowledge of biochemical function and sequence information is found in nearly all classes of enzymes. Thus, there is an urgent need to explore the 1525 orphan enzymes (EC numbers without associated sequences), in order to progressively bridge this unwanted gap. Improving genome annotation could unveil a significant proportion of sequenceless enzymes. Peptide mass mapping and further genome mining would be useful to identify proper sequence for enzymes found in species for which genetic tools are missing. Finally, the whole community must help major public databases to begin addressing the problem of missing or incomplete information.