How it scores
Four explainable axes — never one fragile score.
Each candidate is scored on four independent axes, every one a deterministic, re-runnable computation with its provenance shown.
Manufacturability
GC window, homopolymers, tandem repeats, restriction sites, forbidden motifs.
Host-likeness
A genome-derived K. phaffii codon model (codon usage + %MinMax rhythm + codon-pair bias) that deliberately rejects naive max-CAI over-optimization.
5′ translation initiation
Start-proximal mRNA accessibility — an open start means better initiation.
Protein developability
Length, MW, pI, cysteines, N-glycosylation motifs, hydrophobicity.
EvoCodon
A self-developed, genome-learned codon model.
Candidates are proposed by transparent host heuristics and EvoCodon — a self-developed, genome-learned codon model trained on public K. phaffii genomes that reproduces host-specific codon rhythm beyond frequency-based methods. The learned candidate competes on the same scorecard as every other — it does not auto-win.
Secretion design.
For a secreted protein, Kairos selects a source-traceable secretion leader — e.g. the S. cerevisiae α-mating-factor prepro (UniProt P01149) or the SUC2 invertase signal (UniProt P00724), each carrying its UniProt record and supporting literature — fuses it N-terminally, and designs the coding sequence of the whole construct. Correct by construction: the design encodes exactly signal + target. Kairos chooses a traceable leader and yields a valid construct; it does NOT predict secretion efficiency — that awaits wet-lab data.
Featured run
A Kairos design run on Cytochrome c.
UniProt Q6Q4H8 — a native Komagataella phaffii protein. Twelve reproducible candidates, ranked across all four axes, with the recommended one in the top Pareto tier.
Cited evidence retrieved live from the Kairos knowledge layer — every entry a real, openable source.
AOX1 promoter regulation
Methanol-induced, glucose-repressed (cis/trans regulation) — grounds the expression strategy.
Nitrogen source & MUT pathway
Ammonium sulfate raises MUT / PEX gene expression — tune nitrogen to up-regulate the pathway.
Fed-batch strategy
Glycerol for biomass, then methanol induction — the standard Pichia fermentation rhythm.
Proteolysis risk
Proteolytic degradation of recombinant protein (HSA) in P. pastoris — watch degradation; add inhibitors if needed.
Recommended
| Rank | Method | Pareto tier | Flags |
|---|---|---|---|
| 1 | uniform | top | 1 |
| 2 | host_weighted | top | 1 |
| 3 | gc_balanced | top | 1 |
| 4 | gc_balanced | top | 2 |
| 5 | host_weighted | top | 3 |
extreme_pi flag on the winner is an intrinsic property of the target protein, not a design defect. Sequence withheld in the public report; available to invited collaborators. Engine: Kairos v0.1.0.
FAQ
Yes. Kairos selects a source-traceable secretion signal peptide, fuses it, and designs the full construct's CDS. It chooses the leader and guarantees a valid construct; real secretion efficiency is wet-lab, not predicted.
References
Sources behind the design.
The host heuristics, secretion leaders, and host-likeness model draw on public, traceable literature and reference databases. Each is a real, citable source.
- UniProt P01149 — S. cerevisiae α-mating-factor prepro. UniProt:P01149
- UniProt P00724 — SUC2 invertase signal. UniProt:P00724
- Merkaš M, et al. The MFα signal sequence in yeast-based protein secretion: challenges and innovations. Appl Microbiol Biotechnol, 2025. PMID:40471355
- Aw R, et al. A systematic analysis of the expression of the anti-HIV VRC01 antibody in Pichia pastoris through signal peptide optimization. Protein Expr Purif, 2018. PMID:29601964
- Ahmad M, et al. Efficient Expression of Lactone Hydrolase Cr2zen for Scalable Zearalenone Degradation in Pichia pastoris. Toxins (Basel), 2025. PMID:41591157
- Zha J, et al. Advances in Metabolic Engineering of Pichia pastoris Strains as Powerful Cell Factories. J Fungi (Basel), 2023. PMID:37888283
- Maity N, et al. Statistically Designed Medium Reveals Interactions between Metabolism and Genetic Information Processing for Production of Stable Human Serum Albumin in Pichia pastoris. Biomolecules, 2019. PMID:31590267
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