Biosynthetic gene clusters (BGCs) are co-located genes that encode the biosynthesis of specialized metabolites, an important source of antibiotics, anticancer agents, immunosuppressants, and agricultural bioactives. Deep learning, particularly self-supervised foundation models, has spurred interest in BGC sequence modeling, but evaluation has lagged behind: existing benchmarks often rely on coarse classification over small curated datasets, providing limited discrimination among models and insight into downstream utility. We propose a benchmark-design framework in which an informative benchmark should be discriminative, separating models with statistical confidence, and applicable, spanning scientifically meaningful tasks under different levels of generalization. We instantiate this framework as BGC-Bench, which derives five tasks from MIBiG, ranging from A-domain substrate prediction to BGC-molecule retrieval, evaluates them under genotype- and phenotype-shift splits, includes an active-learning setting for label-scarce discovery, and is easily extensible to new tasks and encoders. BGCs further provide a shared testbed across granularities and modalities: BGC-Bench compares twelve encoders on nucleotide, amino-acid, or Pfam-domain sequences, including compositional baselines for each input type, and combines BGC and chemical encoders for cross-modal retrieval. No single representation dominates: the best granularity depends on the biological scale of the task, and pretrained encoders do not consistently outperform other representations across tasks and splits. Active-learning experiments show that most tasks remain data-limited, encoder rankings change with labeling budget, and acquisition strategies yield modest gains. These results show that BGC model evaluation requires task-diverse, shift-aware benchmarks, and the framework can be generalized to benchmark design beyond BGCs.

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