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.
Zusammenfassung
Hirudin and its variants, as strong inhibitors against thrombin, are present in the saliva of leeches and are recognized as potent anticoagulants.
Warum dies für die Hirudotherapie relevant ist
Diese transkriptomische Studie untersuchte die Produktion der Hirudin-Variante 3 (HV3) – eines potenten Antikoagulans im Blutegelspeichel – unter Verwendung eines rekombinanten Pichia-pastoris-Expressionssystems. Die Forscher untersuchten, wie die Methanolassimilation die Genexpression beeinflusst, und stellten fest, dass eine Hochregulierung des zentralen Kohlenstoff-, Energie- und Aminosäurestoffwechsels potenziell die HV3-Ausbeute in der Fermentation verbessern könnte. Diese Forschung ist für die American Society of Hirudotherapy hochrelevant, da sie direkt auf die biotechnologische Produktion und Ausbeuteoptimierung eines Schlüsseltherapeutikums aus Blutegeln eingeht. Allerdings konzentriert sich die Studie strikt auf Fermentationsoptimierung und genetische Expression und nicht auf klinische Hirudotherapie oder lebende Blutegelanwendung.
Zitation
Transcriptomic Analysis of the Influence of Methanol Assimilation on the Gene Expression in the RecombinantProducing Hirudin Variant 3
Li T et al. · Genes, 2019
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