CONCLUSIONS: Crucially, this study demonstrates that LLMs still have to be improved to become the gold standard tool over BLASTp in mainstream enzyme annotation routines. On the other hand, LLMs can provide good predictions for more difficult-to-annotate enzymes, particularly when the identity between the query sequence and the reference database falls below 25%. Our results reinforce the claim that BLASTp and LLM models complement each other and can be more effective when used …