Synthesis of an antiviral drug precursor from chitin using a saprophyte as a whole-cell catalyst
Identifieur interne : 002422 ( Ncbi/Checkpoint ); précédent : 002421; suivant : 002423Synthesis of an antiviral drug precursor from chitin using a saprophyte as a whole-cell catalyst
Auteurs : Matthias G. Steiger [Autriche] ; Astrid R. Mach-Aigner [Autriche] ; Rita Gorsche [Autriche] ; Erwin E. Rosenberg [Autriche] ; Marko D. Mihovilovic [Autriche] ; Robert L. Mach [Autriche]Source :
- Microbial Cell Factories [ 1475-2859 ] ; 2011.
Abstract
Recent incidents, such as the SARS and influenza epidemics, have highlighted the need for readily available antiviral drugs. One important precursor currently used for the production of Relenza, an antiviral product from GlaxoSmithKline, is N-acetylneuraminic acid (NeuNAc). This substance has a considerably high market price despite efforts to develop cost-reducing (biotechnological) production processes.
In this study, we introduced two enzymes from bacterial origin into
This study is a proof of concept for the possibility to engineer in a filamentous fungus a bacterial enzyme cascade, which is fully functional. Furthermore, it provides the basis for the development of a process for NeuNAc production as well as a general prospective design for production processes that use saprophytes as whole-cell catalysts.
The online version of this article (doi:10.1186/1475-2859-10-102) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1475-2859-10-102
PubMed: 22141613
PubMed Central: 3245449
Affiliations:
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PMC:3245449Le document en format XML
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<series><title level="j">Microbial Cell Factories</title>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Recent incidents, such as the SARS and influenza epidemics, have highlighted the need for readily available antiviral drugs. One important precursor currently used for the production of Relenza, an antiviral product from GlaxoSmithKline, is N-acetylneuraminic acid (NeuNAc). This substance has a considerably high market price despite efforts to develop cost-reducing (biotechnological) production processes. <italic>Hypocrea jecorina</italic>
(<italic>Trichoderma reesei</italic>
) is a saprophyte noted for its abundant secretion of hydrolytic enzymes and its potential to degrade chitin to its monomer N-acetylglucosamine (GlcNAc). Chitin is considered the second most abundant biomass available on earth and therefore an attractive raw material.</p>
</sec>
<sec><title>Results</title>
<p>In this study, we introduced two enzymes from bacterial origin into <italic>Hypocrea</italic>
, which convert GlcNAc into NeuNAc via N-acetylmannosamine. This enabled the fungus to produce NeuNAc from the cheap starting material chitin in liquid culture. Furthermore, we expressed the two recombinant enzymes as GST-fusion proteins and developed an enzyme assay for monitoring their enzymatic functionality. Finally, we demonstrated that <italic>Hypocrea</italic>
does not metabolize NeuNAc and that no NeuNAc-uptake by the fungus occurs, which are important prerequisites for a potential production strategy.</p>
</sec>
<sec><title>Conclusions</title>
<p>This study is a proof of concept for the possibility to engineer in a filamentous fungus a bacterial enzyme cascade, which is fully functional. Furthermore, it provides the basis for the development of a process for NeuNAc production as well as a general prospective design for production processes that use saprophytes as whole-cell catalysts.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1475-2859-10-102) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Autriche</li>
</country>
<region><li>Vienne (Autriche)</li>
</region>
<settlement><li>Vienne (Autriche)</li>
</settlement>
</list>
<tree><country name="Autriche"><noRegion><name sortKey="Steiger, Matthias G" sort="Steiger, Matthias G" uniqKey="Steiger M" first="Matthias G" last="Steiger">Matthias G. Steiger</name>
</noRegion>
<name sortKey="Gorsche, Rita" sort="Gorsche, Rita" uniqKey="Gorsche R" first="Rita" last="Gorsche">Rita Gorsche</name>
<name sortKey="Mach Aigner, Astrid R" sort="Mach Aigner, Astrid R" uniqKey="Mach Aigner A" first="Astrid R" last="Mach-Aigner">Astrid R. Mach-Aigner</name>
<name sortKey="Mach, Robert L" sort="Mach, Robert L" uniqKey="Mach R" first="Robert L" last="Mach">Robert L. Mach</name>
<name sortKey="Mihovilovic, Marko D" sort="Mihovilovic, Marko D" uniqKey="Mihovilovic M" first="Marko D" last="Mihovilovic">Marko D. Mihovilovic</name>
<name sortKey="Rosenberg, Erwin E" sort="Rosenberg, Erwin E" uniqKey="Rosenberg E" first="Erwin E" last="Rosenberg">Erwin E. Rosenberg</name>
<name sortKey="Steiger, Matthias G" sort="Steiger, Matthias G" uniqKey="Steiger M" first="Matthias G" last="Steiger">Matthias G. Steiger</name>
</country>
</tree>
</affiliations>
</record>
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