We have completed a systematic survey of Drosophila melanogaster enzymes, improving the coverage and accuracy of their functional Gene Ontology annotations in FlyBase and collaborating databases. We made >5,000 changes to manual Gene Ontology annotations by reviewing information from the literature and consulting expert databases, resulting in the final verification of 3,708 Drosophila enzyme-encoding genes. Herein, we present an overview of the enzyme landscape in Drosophila, including insights on enzyme paralogs, pseudoenzymes, and enzymatic complexes, and compare these with corresponding datasets for yeast and humans. We also show how the presentation of enzyme data on FlyBase gene reports has been enhanced, including the addition of Enzyme Commission (EC) information and RHEA reaction graphics. For each class of enzyme, we have created a "Gene Group" page in FlyBase to tabulate the group members and facilitate access to related information and tools. Together, this work provides a comprehensive enzyme resource to serve the Drosophila research community and beyond. As a practical example of its utility, we used our improved dataset to update the FlyCyc model of Drosophila metabolism.
Keywords: Drosophila; FlyBase; FlyCyc; Gene Ontology; enzymes; functional annotation; metabolism; paralogs; pseudoenzymes.
© The Author(s) 2025. Published by Oxford University Press on behalf of The Genetics Society of America.