Transcriptomic Analysis of the Influence of Methanol Assimilation on the Gene Expression in the RecombinantProducing Hirudin Variant 3
Research article published in Genes (2019)
Abstract
Hirudin and its variants, as strong inhibitors against thrombin, are present in the saliva of leeches and are recognized as potent anticoagulants. However, their yield is far from the clinical requirement up to now. In this study, the production of hirudin variant 3 (HV3) was successfully realized by cultivating the recombinant Pichia pastoris GS115/pPIC9K-hv3 under the regulation of the promoter of AOX1 encoding alcohol oxidase (AOX). The antithrombin activity in the fermentation broth reached the maximum value of 5000 ATU/mL. To explore an effective strategy for improving HV3 production in the future, we investigated the influence of methanol assimilation on the general gene expression in this recombinant by transcriptomic study. The results showed that methanol was partially oxidized into CO2, and the rest was converted into glycerone-P which subsequently entered into central carbon metabolism, energy metabolism, and amino acid biosynthesis. However, the later metabolic processes were almost all down-regulated. Therefore, we propose that the up-regulated central carbon metabolism, energy, and amino acid metabolism should be beneficial for methanol assimilation, which would accordingly improve the production of HV3.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirudin and its variants, as strong inhibitors against thrombin, are present in the saliva of leeches and are recognized as potent anticoagulants.
Por qué esto importa para la hirudoterapia
This transcriptomic study examined the production of hirudin variant 3 (HV3)—a potent anticoagulant found in leech saliva—using a recombinant Pichia pastoris expression system. The researchers investigated how methanol assimilation influences gene expression, finding that up-regulating central carbon, energy, and amino acid metabolism could potentially improve HV3 yield in fermentation. This research is highly relevant to the American Society of Hirudotherapy as it directly addresses the biotechnological production and yield optimization of a key leech-derived therapeutic. However, the study focuses strictly on fermentation optimization and genetic expression rather than clinical hirudotherapy or live leech application.
Citación
Transcriptomic Analysis of the Influence of Methanol Assimilation on the Gene Expression in the RecombinantProducing Hirudin Variant 3
Li T et al. · Genes, 2019
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026