Leveraging Large Language Models for enzymatic reaction prediction and characterization

Abstract: Predicting enzymatic reactions is crucial for applications in biocatalysis, metabolic engineering, and drug discovery, yet it remains a complex and resource-intensive task. LLMs have recently demonstrated remarkable success in various scientific domains, e.g., through their ability to generalize knowledge, reason over complex structures, and leverage in-context learning strategies. In this study, we systematically evaluate the capability of LLMs, particularly the Llama-3.1 family (8B and 70B), across three core biochemical tasks: Enzyme Commission number prediction, forward synthesis, and retrosynthesis. We compare single-task and multitask learning strategies, employing parameter-efficient fine-tuning via LoRA adapters. Additionally, we assess performance across different data regimes to explore their adaptability in low-data settings. Our results demonstrate that fine-tuned LLMs capture biochemical knowledge, with multitask learning enhancing forward- and retrosynthesis predictions by leveraging shared enzymatic information. We also identify key limitations, for example challenges in hierarchical EC classification schemes, highlighting areas for further improvement in LLM-driven biochemical modeling.