The ω-transaminase engineering database (oTAED): A navigation tool in protein sequence and structure space

Area of Science:

• Biotechnology
• Enzyme Engineering
• Structural Biology

Background:

• ω-transaminases (ω-TAs) are crucial biocatalysts with biotechnological applications.
• Existing data on ω-TAs are fragmented across various resources.
• Fold types I and IV represent significant families of ω-TAs.

Purpose of the Study:

• To establish a comprehensive, publicly accessible database (oTAED) for ω-TAs.
• To integrate sequence and structure data with a standardized numbering scheme.
• To facilitate the analysis of conserved positions and substrate specificity.

Main Methods:

• Database creation integrating sequence and structure information.
• Classification of ω-TAs based on fold type and sequence similarity.
• Development of standard numbering schemes for Fold types I and IV.
• Systematic literature review of substrate specificity and stereoselectivity determinants.

Main Results:

• The oTAED contains 67,210 proteins (114,655 sequences) across 169 homologous families.
• Identified 44 (Fold I) and 39 (Fold IV) conserved positions, including known catalytic residues.
• Standard numbering schemes revealed structural equivalence of positions across different ω-TAs.
• Literature analysis identified positions mediating substrate specificity and stereoselectivity.

Conclusions:

• The oTAED serves as a valuable resource for enzyme engineering and ω-TA discovery.
• Standardized numbering aids literature analysis, annotation, and prediction of mutation sites.
• The database supports navigation of ω-TA sequence space for selecting enzymes with desired properties.