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Article: Studies of the production of fungal polyketides in Aspergillus nidulans by using systems biology tools

TitleStudies of the production of fungal polyketides in Aspergillus nidulans by using systems biology tools
Authors
Issue Date2009
Citation
Applied And Environmental Microbiology, 2009, v. 75 n. 7, p. 2212-2220 How to Cite?
AbstractMany filamentous fungi produce polyketide molecules with great significance as human pharmaceuticals; these molecules include the cholesterol-lowering compound lovastatin, which was originally isolated from Aspergillus terreus. The chemical diversity and potential uses of these compounds are virtually unlimited, and it is thus of great interest to develop a well-described microbial production platform for polyketides. Using genetic engineering tools available for the model organism Aspergillus nidulans, we constructed two recombinant strains, one expressing the Pénicillium griseofulvum 6-methylsalicylic acid (6-MSA) synthase gene and one expressing the 6-MSA synthase gene and overexpressing the native xylulose-5-phosphate phosphoketolase gene (xpkA) for increasing the pool of polyketide precursor levels. The physiology of the recombinant strains and that of a reference wild-type strain were characterized on glucose, xylose, glycerol, and ethanol media in controlled bioreactors. Glucose was found to be the preferred carbon source for 6-MSA production, and 6-MSA concentrations up to 455 mg/liter were obtained for the recombinant strain harboring the 6-MSA gene. Our findings indicate that overexpression of xpkA does not directly improve 6-MSA production on glucose, but it is possible, if the metabolic flux through the lower part of glycolysis is reduced, to obtain quite high yields for conversion of sugar to 6-MSA. Systems biology tools were employed for in-depth analysis of the metabolic processes. Transcriptome analysis of 6-MSA-producing strains grown on glucose and xylose in the presence and absence of xpkA overexpression, combined with flux and physiology data, enabled us to propose an xpkA-msaS interaction model describing the competition between biomass formation and 6-MSA production for the available acetyl coenzyme A. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/181254
ISSN
2015 Impact Factor: 3.823
2015 SCImago Journal Rankings: 1.891
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPanagiotou, Gen_US
dc.contributor.authorAndersen, MRen_US
dc.contributor.authorGrotkjaer, Ten_US
dc.contributor.authorRegueira, TBen_US
dc.contributor.authorNielsen, Jen_US
dc.contributor.authorOlsson, Len_US
dc.date.accessioned2013-02-21T02:03:31Z-
dc.date.available2013-02-21T02:03:31Z-
dc.date.issued2009en_US
dc.identifier.citationApplied And Environmental Microbiology, 2009, v. 75 n. 7, p. 2212-2220en_US
dc.identifier.issn0099-2240en_US
dc.identifier.urihttp://hdl.handle.net/10722/181254-
dc.description.abstractMany filamentous fungi produce polyketide molecules with great significance as human pharmaceuticals; these molecules include the cholesterol-lowering compound lovastatin, which was originally isolated from Aspergillus terreus. The chemical diversity and potential uses of these compounds are virtually unlimited, and it is thus of great interest to develop a well-described microbial production platform for polyketides. Using genetic engineering tools available for the model organism Aspergillus nidulans, we constructed two recombinant strains, one expressing the Pénicillium griseofulvum 6-methylsalicylic acid (6-MSA) synthase gene and one expressing the 6-MSA synthase gene and overexpressing the native xylulose-5-phosphate phosphoketolase gene (xpkA) for increasing the pool of polyketide precursor levels. The physiology of the recombinant strains and that of a reference wild-type strain were characterized on glucose, xylose, glycerol, and ethanol media in controlled bioreactors. Glucose was found to be the preferred carbon source for 6-MSA production, and 6-MSA concentrations up to 455 mg/liter were obtained for the recombinant strain harboring the 6-MSA gene. Our findings indicate that overexpression of xpkA does not directly improve 6-MSA production on glucose, but it is possible, if the metabolic flux through the lower part of glycolysis is reduced, to obtain quite high yields for conversion of sugar to 6-MSA. Systems biology tools were employed for in-depth analysis of the metabolic processes. Transcriptome analysis of 6-MSA-producing strains grown on glucose and xylose in the presence and absence of xpkA overexpression, combined with flux and physiology data, enabled us to propose an xpkA-msaS interaction model describing the competition between biomass formation and 6-MSA production for the available acetyl coenzyme A. Copyright © 2009, American Society for Microbiology. All Rights Reserved.en_US
dc.languageengen_US
dc.relation.ispartofApplied and Environmental Microbiologyen_US
dc.subject.meshAcyltransferases - Geneticsen_US
dc.subject.meshAldehyde-Lyases - Geneticsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnticholesteremic Agents - Metabolismen_US
dc.subject.meshAspergillus Nidulans - Genetics - Growth & Development - Metabolismen_US
dc.subject.meshBioreactorsen_US
dc.subject.meshBiosynthetic Pathways - Geneticsen_US
dc.subject.meshCarbohydrate Metabolismen_US
dc.subject.meshFermentationen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshGenes, Fungalen_US
dc.subject.meshGenetic Engineeringen_US
dc.subject.meshHumansen_US
dc.subject.meshLigases - Geneticsen_US
dc.subject.meshMacrolides - Metabolismen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshMultienzyme Complexes - Geneticsen_US
dc.subject.meshOxidoreductases - Geneticsen_US
dc.subject.meshPenicillium - Geneticsen_US
dc.subject.meshRecombination, Geneticen_US
dc.subject.meshSystems Biology - Methodsen_US
dc.subject.meshUnited Statesen_US
dc.titleStudies of the production of fungal polyketides in Aspergillus nidulans by using systems biology toolsen_US
dc.typeArticleen_US
dc.identifier.emailPanagiotou, G: gipa@hku.hken_US
dc.identifier.authorityPanagiotou, G=rp01725en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/AEM.01461-08en_US
dc.identifier.pmid19168657-
dc.identifier.scopuseid_2-s2.0-63849107219en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-63849107219&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume75en_US
dc.identifier.issue7en_US
dc.identifier.spage2212en_US
dc.identifier.epage2220en_US
dc.identifier.isiWOS:000264549400047-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPanagiotou, G=8566179700en_US
dc.identifier.scopusauthoridAndersen, MR=15841796100en_US
dc.identifier.scopusauthoridGrotkjaer, T=6506918583en_US
dc.identifier.scopusauthoridRegueira, TB=25825375400en_US
dc.identifier.scopusauthoridNielsen, J=7404066338en_US
dc.identifier.scopusauthoridOlsson, L=7203077540en_US

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