American Society of Hirudotherapy

Coexpression of BiP increased antithrombotic hirudin production in recombinant Saccharomyces cerevisiae

Comparative study published in J Biotechnol (2003)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Observational studySalivary PharmacologyDrug DevelopmentKim MD et al. · J Biotechnol, 2003

Abstract

In order to increase a production level of antithrombotic hirudin, BiP was simultaneously expressed in recombinant Saccharomyces cerevisiae strains carrying ten and 15 copies of the hirudin expression cassette integrated in the chromosome. Coexpression of BiP greatly enhanced both cell growth and hirudin production in recombinant S. cerevisiae. Maximum hirudin concentration of 36 mg l(-1) was obtained from batch culture of the ten copy-number transformant concomitantly harboring an episomal copy of the BiP gene under the control of the GAL1 promoter, which is corresponding to a 2.5-fold increase compared with the control strain carrying the genomic BiP gene only. The mean size of the recombinant yeast cells expressing the BiP gene remained at a relatively constant level compared with the control strains of which size increased after the onset of hirudin expression by the GAL10 promoter.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsCell DivisionCells, CulturedEscherichia coliFibrinolytic AgentsFungal ProteinsGalactoseGene Expression Regulation, FungalGlucoseHSP70 Heat-Shock ProteinsHirudinsMutagenesis, InsertionalRecombinant Proteins

Summary

Coexpression of BiP chaperone with hirudin expression cassette in S. cerevisiae enhanced cell growth and hirudin production 2.5-fold; maximum 36 mg/L from batch culture.

Why This Matters for Hirudotherapy

This study examined whether coexpressing BiP (a chaperone protein) in recombinant Saccharomyces cerevisiae could enhance production of antithrombotic hirudin, achieving a maximum concentration of 36 mg/L—a 2.5-fold increase over control strains using a ten-copy transformant with episomal BiP under the GAL1 promoter. This work is directly relevant to ASH and hirudotherapy because hirudin is the primary anticoagulant component of the medicinal leech secretome, and improving recombinant production methods could support more reliable supply of this key therapeutic protein for both research and potential clinical use. The findings demonstrate a feasible biotechnological strategy to increase yields of this leech-derived anticoagulant. However, this is a production optimization study in engineered yeast, not a clinical or in vivo efficacy evaluation, so it does not address therapeutic outcomes or safety in hirudotherapy contexts.

Citation

Coexpression of BiP increased antithrombotic hirudin production in recombinant Saccharomyces cerevisiae.

Kim MD et al. · J Biotechnol, 2003

DOI

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