From Computational Prioritization to Sustainable Supply: A Two-Axis Framework for Marine Invertebrate-Associated Natural Products and Derivatives

Marine invertebrates and their microbial partners provide distinctive chemical scaffolds, but computational prioritization alone can overstate translational progress when experimental support and material supply remain limited. This critical narrative review proposes a linked-record framework for evaluating exact entity-indication pairs on two independent axes: therapeutic-evaluation stage (E1, in silico, to E4, human intervention) and production readiness (S1, discovery access, to S4, GMP or commercial manufacture). E records the highest stage documented in the reviewed sources, not evidence strength or therapeutic success. Computational contribution, evidence direction, study quality, provenance, and scenario-specific supply adequacy remain separate attributes; E and S are not combined into a composite score. Contrasting lineages involving halichondrin B and eribulin, (+)-aeroplysinin-1, a sea-star steroid, acanthomanzamine C, cynthichlorine, gukulenin A, and meridianin mixtures illustrate how uncertain chronology, test-article mismatch, incomplete validation, and poorly characterized production routes affect interpretation. A worked mass balance distinguishes physical access from the amount required for a defined experiment. Supply-by-design therefore integrates identity, route feasibility, demand, ecological constraints, and access obligations at nomination. The framework is preliminary and requires independent reliability and prospective utility testing.