Uricase Protease-Site Proxy for Shio-Koji (comp-001)¶

The exploitable weakness is straightforward: a secreted UOX payload is useless if shio-koji proteases destroy its activity before delivery. COMP-001 does not answer whether that happens. It preserves the narrower computational prior that can be established from the available inputs.

Verdict: proxy only; empirical protease risk is unresolved.

What the computation establishes¶

Deterministic computational audit: The fixed Q00511 sequence contains 215 adjacent pairs matching the legacy ALP P1 filter, 97 matching the legacy NPr P1′ filter, and 44 matching the legacy acid-protease P1/P1′ filter. The AlphaFold model reports high confidence across Q00511: mean pLDDT 97.14, minimum 80.50.

Those residue arrays lack claim-level provenance establishing them as exhaustive protease-specificity rules. They are therefore fixed legacy filters, not verified cleavage rules. The complete pair inventory and exact local pLDDT windows are in the COMP-001 artifact.

What remains unknown¶

pLDDT measures prediction confidence. It does not measure solvent exposure, burial, protease access, cleavage probability, time-integrated degradation, retained UOX activity, or performance in a ferment. High pLDDT around a filter match cannot support a LOW-risk or survival conclusion.

The result applies only to the proposed Q00511-in-shio-koji route. It neither validates nor weakens uricase as an intervention, another delivery route, or another research track.

Delivery decision¶

The candidate route is UOX produced by engineered A. oryzae and delivered in a shio-koji product. COMP-001 supplies no production, secretion, dose, shelf-life, gastric-transit, or target-compartment exposure claim. Chassis work should proceed only alongside direct measurement of the actual expressed product.

Discriminating experiment¶

The §1.10 shio-koji retained-activity assay remains the feasibility gate. Measure UOX abundance and retained urate-oxidation activity at day 0, 7, and 14 in the actual ferment, with matched no-protease and heat-inactivated controls. A favorable result advances this route; activity loss redirects formulation, host, secretion, or delivery design without rejecting the wider uricase hypothesis.