Secretion design: source-traceable signal peptides

Pichia is a secretion workhorse. Many proteins of interest are not meant to stay inside the cell — they need to be routed through the secretory pathway. Kairos now designs secreted constructs, not just intracellular coding sequences: it chooses a signal peptide, fuses it to the target, and designs the CDS of the entire construct.

A chosen, traceable leader

For a secreted protein, Kairos selects a source-traceable secretion leader. Each candidate leader carries its UniProt record and supporting literature. Two leaders Kairos works with today:

• The S. cerevisiae α-mating-factor prepro peptide (UniProt P01149) — the most widely used secretion signal in Pichia expression.
• The SUC2 invertase signal (UniProt P00724) — an alternative, well-characterized leader.

Each is a real, citable biological part — not a generated sequence. Kairos's job is to choose appropriately and fuse it correctly.

Correct by construction

The design step fuses the selected leader N-terminally to the target, then designs the coding sequence of the entire construct. The result is verified: the design encodes exactly signal + target, in-frame, with the leader in its natural reading frame. This guarantee is mechanical, not probabilistic — you can re-run the check on the printed sequence.

What it does, and what it does not

Kairos chooses a traceable leader and yields a valid construct. It does not predict secretion efficiency — that depends on folding, glycosylation, host strain, and culture conditions, and awaits wet-lab data. The design provenance keeps a slot for that feedback.

References

The secretion leaders Kairos works with are real, citable biological parts — each carrying its UniProt record and supporting literature.

1. UniProt P01149 — S. cerevisiae α-mating-factor prepro. UniProt:P01149
2. UniProt P00724 — SUC2 invertase signal. UniProt:P00724
3. Merkaš M, et al. The MFα signal sequence in yeast-based protein secretion: challenges and innovations. Appl Microbiol Biotechnol, 2025. PMID:40471355
4. 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
5. Bhakta V, et al. Expression and purification of a broad-spectrum human protease inhibitor in Pichia pastoris. Biochem Biophys Rep, 2025. PMID:40607491