Open Enzyme¶
An open source library of food-grade engineered microbial strains — each producing a therapeutic enzyme, each growable at home, each freely available to anyone.
Status: Phase 0 — Research & Design
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 engineering a complementary approach: gut-lumen degradation via an enzyme-producing probiotic strain that never needs to be absorbed.
Platform Thesis¶
One engineered Aspergillus oryzae koji strain expressing uricase + NLRP3 inhibitors, 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, and already co-produces NLRP3-suppressing compounds (kojic acid, 3–5 g/L natively) as a byproduct of fermentation. The platform is koji-first: A. oryzae is the primary host, with S. cerevisiae retained for specific modules where yeast expression is better characterized. (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.
Two parallel outputs: The strain library is one synthesis from a broader discovery engine — a chokepoint-based methodology for mapping every vector that causes, treats, or mitigates a given disease. The discovery engine also produces a repurposing surface: FDA-approved drugs that hit relevant chokepoints but were never clinically tested for the target disease (e.g., zileuton at CP6a, disulfiram at CP6b, avacopan at CP0). (source: etc/open-enzyme-vision.md, §2)
Platform positioning: Open Enzyme is a food-derived, multi-target NLRP3 pathway modulator platform — not an attempt to produce a food-grade analog of the direct NLRP3 inhibitor class (MCC950, dapansutrile, oridonin). (source: etc/open-enzyme-vision.md, §10)
First Targets¶
| Target | Condition | Platform | Status |
|---|---|---|---|
| Uricase | Gout / hyperuricemia | S. cerevisiae or A. oryzae | Design phase |
| Lipase + protease + amylase | EPI (exocrine pancreatic insufficiency) | A. oryzae koji | Design phase |
| NLRP3 inhibitors | Gout flare suppression | A. oryzae co-production | Design phase |
New This Week (2026-05-17)¶
This sweep propagated three clinical-surface findings from trigger files into the research wiki:
BHB active-flare contraindication propagated to nlrp3-exploit-map.md — the "ketosis paradox resolved" framing (BHB suppresses NLRP3 while uricase handles UA) is correct for prophylaxis, but BHB/ketosis is NOT a rescue intervention during active flare. Transient ketotic UA rise of 5–10% can compound the flare. Suspend ketosis + intermittent fasting during active flares; resume after 1–2 weeks. (source: gout-action-guide.md)
Anakinra SC for acute gout flare propagated to nlrp3-exploit-map.md CP5a section and colchicine.md comparison table — 100 mg/day × 3 days SC in thigh/abdomen off-label for gout. Same IL-1R1 chokepoint as canakinumab but ~100× cheaper (~$900/flare) with cleaner cumulative burden vs prednisone over decades of recurrent flares. Faster onset than prednisone, narrower mechanism, none of the bone/glucose/adrenal/mood effects. (source: gout-action-guide.md, gout-clinical-pipeline.md)
Topical CBD+THC acute-flare protocol propagated to nlrp3-exploit-map.md, supplements-stack.md, and GRAPH.md — 1:1 CBD:THC (high-mg/oz) applied to affected joint + ice cycling. CB2-mediated NLRP3 suppression + TRPV1 desensitization. For recurrent-flare patients with cumulative steroid burden, may reduce prednisone need. Jurisdiction-dependent. (source: cannabinoids-terpenes.md, gout-action-guide.md)
Plasmidsaurus QC pipeline and consumer SNP data-quality gap already well cross-referenced in validation-experiments.md, personal-genome-protocol.md, and genotype-informed-supplement-workflow.md — no propagation needed. (source: engineered-koji-protocol.md, gout-action-guide.md)
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¶
The Synthesis Queue captures cross-document connections, proposed experiments, and open questions. Updated by the sweep daemon as new research lands. 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.