Open Enzyme¶
An open source effort to disrupt the gout / NLRP3 / urate-disposal cascade — mapping every chokepoint in the disease and finding the right intervention for each, then building the ones that can be made food-grade and grown at home.
Status: Phase 0 — Research & Design
Have gout? Want to know what to do? → Start with the Gout Action Guide — organized by situation (today / this month / this year), it translates the research below into action. → Prefer a patient-friendly companion site? gout.care is the plain-language translation of this research, written for people living with gout rather than the PhD-research audience.
The Problem¶
The human body is missing an enzyme. Urate oxidase (uricase) was lost ~15 million years ago in the primate lineage. Every other mammal degrades uric acid to allantoin; we accumulate it. The result: gout, kidney stones, and chronic inflammation — affecting ~10 million Americans.
The standard fix (allopurinol) reduces production. We're mapping the entire cascade — production, renal and gut handling, crystal formation, and the NLRP3-driven inflammation that follows — and matching each chokepoint to the cheapest intervention that hits it, whether engineered, repurposed, dietary, or behavioral.
Platform Thesis¶
The mission is the chokepoint map; the strain library is one output of it. We map every vector that causes, treats, or mitigates gout, then build interventions chokepoint-by-chokepoint. Chassis is downstream of chokepoint — no single organism reaches every target.
Highest-priority chassis: engineered koji. One engineered Aspergillus oryzae strain expressing uricase plus a multi-cassette payload (carnosine, lactoferrin, DAF SCR1-4 in the endgame), fermented on rice bran, positioned as an adjunct to allopurinol — not a monotherapy replacement.
Why koji? A. oryzae is GRAS, natively secretes enzymes at high titer, survives GI transit in solid-substrate form, harmoniously hits multiple chokepoints in one strain, and is home-fermentable — which matches the open-source, democratized-access positioning. It also co-produces NLRP3-suppressing compounds (kojic acid, 3–5 g/L natively) as a fermentation byproduct. (source: etc/open-enzyme-vision.md, §4)
Why gut-lumen? ~⅓ of uric acid is secreted into the gut via ABCG2. Degrading it there doesn't require systemic absorption — the enzyme never needs to cross the intestinal wall. ALLN-346 (Allena Pharmaceuticals) proved this concept clinically.
Beyond koji. Chokepoints koji can't reach — renal URAT1, kidney macrophages, intra-articular crystals, the acute flare window — are pursued through other chassis (kidney-tropic siRNA, engineered live biotherapeutics, purine-degrading bacteria, mRNA-IL-1RA pulse, intra-articular uricase, phage modulation), tracked in Chassis-Pending Interventions. The discovery engine also surfaces a repurposing surface: FDA-approved drugs that hit relevant chokepoints but were never clinically tested for gout (e.g., zileuton at CP6a, disulfiram at CP6b, avacopan at CP0). (source: etc/open-enzyme-vision.md, §1–2)
Koji-track positioning: within the koji chassis specifically, Open Enzyme is a food-derived, multi-target NLRP3 pathway modulator — not an attempt to make a food-grade analog of the direct NLRP3 inhibitor class (MCC950, dapansutrile, oridonin). (source: etc/open-enzyme-vision.md, §10)
First Targets¶
| Target | Condition | Chassis | Status |
|---|---|---|---|
| Uricase | Gout / hyperuricemia | A. oryzae koji (primary); S. cerevisiae for characterized modules | Design phase |
| Carnosine + lactoferrin + DAF SCR1-4 | NLRP3 / complement priming, urate handling | A. oryzae co-expression (multi-cassette endgame) | Design phase |
| Lipase + protease + amylase | EPI (exocrine pancreatic insufficiency) | A. oryzae koji | Design phase |
Where to Start¶
New to the project? → Open Enzyme Vision — the problem, insight, and platform vision (10 min read)
Scientist evaluating the thesis? → Cross-Validation — rigorous stress test: feasibility ratings, risk matrix, clinical bridges
Engineer interested in the construct design?
→ Protein Engineering Strategy — SB-1 / BAL-1 / OPT-1 mutation tiers with full lookup table
→ Engineered Yeast Uricase Proposal — full S. cerevisiae construct design
→ Koji Construct Design — A. oryzae uricase expression
Clinician or pharma reviewer?
→ Gout Deep Dive — full pathophysiology and current standard of care
→ GI Survival Prediction — transit model and bioavailability estimates
Latest Synthesis¶
Research lands continuously: a multi-pass sweep daemon propagates each new finding across every cross-referenced page and emits cross-document connections, contradictions, proposed experiments, and open questions. The live action queue (one file per finding) lives in the synthesis queue on GitHub. Cheapest validated experiments are prioritized first.
Evidence Standard¶
All claims are tagged with evidence level: Clinical Trial · Animal Model · In Vitro · Mechanistic Extrapolation. This library is written for PhD scientists. We distinguish proven from speculative and do not oversell.