The chromosome-level genome of Mesobuthus martensii provides insights into its evolution and the diversity of venom peptides

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  The chromosome-level genome of Mesobuthus martensii provides insights into its evolution and the diversity of venom peptides Abstract Mesobuthus martensii , the source species of the traditional Chinese medicine “Quanxie”, has long been utilized for its therapeutic properties. Venom peptides are recognized as the major active molecular basis of these pharmacological activities. Despite this, their development as therapeutic agents remains poorly explored. In this study, we performed an integrated multi-omics investigation to systematically explore the venom peptides of Mesobuthus martensii . We generated a chromosome-level genome assembly of Mesobuthus martensii using third-generation sequencing technologies, yielding a genome size of 1.08 Gb with a contig N50 of 46.46 Mb. Integrated genomic and transcriptomic analyses led to the identification of 51 putative novel venom peptide candidates. From the broader venom peptide set, five lysine- and arginine-rich candidates were select...

Molecular engineering of Komagataella phaffii for venom toxin production

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Molecular engineering of Komagataella phaffii for venom toxin production

Abstract

Animal venoms constitute a rich source of bioactive peptides and proteins with high target specificity, representing valuable scaffolds for therapeutic development. However, the biotechnological exploitation of venom-derived toxins is limited by challenges in achieving efficient, scalable, and reproducible production. Native venom extraction is constrained by low yields and biological variability, making recombinant platforms essential. Yet, most venom toxins are cysteine-rich peptides with complex disulfide bond architectures and stringent structure–function relationships, posing significant challenges to heterologous expression. Inefficient folding, proteolysis, and secretion bottlenecks frequently compromise functional yield. Among microbial hosts, Komagataella phaffii has emerged as a robust system combining eukaryotic protein processing with high cell-density fermentation and cost-effective cultivation. Its oxidative secretory pathway, strong and regulatable promoters, and suitability for strain engineering make it particularly attractive for producing disulfide-rich toxins. This review provides a critical analysis of recombinant venom toxin production in K. phaffii, focusing on molecular and bioprocess determinants of expression performance. We discuss post-translational modifications, yields, and bioactivity, as well as promoter selection and secretion signal optimization. By integrating data across toxin families, we identify recurring technical bottlenecks and highlight engineering approaches to enhance venom biomanufacturing within microbial biotechnology frameworks.

Cordeiro, F.A., Bordon, K.d.C.F., Covali-Pontes, H.R. et al. Molecular engineering of Komagataella phaffii for venom toxin production. Appl Microbiol Biotechnol (2026). https://doi.org/10.1007/s00253-026-13850-w