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dc.contributor.authorGummerlich, Nils
dc.contributor.authorRebets, Yuriy
dc.contributor.authorPaulus, Constanze
dc.contributor.authorZapp, Josef
dc.contributor.authorLuzhetskyy, Andriy
dc.date.accessioned2021-01-13T15:12:49Z
dc.date.available2021-01-13T15:12:49Z
dc.date.issued2020-12-19
dc.identifier.citationMicroorganisms. 2020 Dec 19;8(12):2034. doi: 10.3390/microorganisms8122034.en_US
dc.identifier.issn2076-2607
dc.identifier.pmid33352664
dc.identifier.doi10.3390/microorganisms8122034
dc.identifier.urihttp://hdl.handle.net/10033/622677
dc.description.abstractNatural products are an important source of novel investigational compounds in drug discovery. Especially in the field of antibiotics, Actinobacteria have been proven to be a reliable source for lead structures. The discovery of these natural products with activity- and structure-guided screenings has been impeded by the constant rediscovery of previously identified compounds. Additionally, a large discrepancy between produced natural products and biosynthetic potential in Actinobacteria, including representatives of the order Pseudonocardiales, has been revealed using genome sequencing. To turn this genomic potential into novel natural products, we used an approach including the in-silico pre-selection of unique biosynthetic gene clusters followed by their systematic heterologous expression. As a proof of concept, fifteen Saccharothrixespanaensis genomic library clones covering predicted biosynthetic gene clusters were chosen for expression in two heterologous hosts, Streptomyceslividans and Streptomycesalbus. As a result, two novel natural products, an unusual angucyclinone pentangumycin and a new type II polyketide synthase shunt product SEK90, were identified. After purification and structure elucidation, the biosynthetic pathways leading to the formation of pentangumycin and SEK90 were deduced using mutational analysis of the biosynthetic gene cluster and feeding experiments with 13C-labelled precursors.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectActinobacteriaen_US
dc.subjectangucyclinoneen_US
dc.subjectbiosynthesisen_US
dc.subjectheterologous expressionen_US
dc.subjectnatural productsen_US
dc.titleTargeted Genome Mining-From Compound Discovery to Biosynthetic Pathway Elucidation.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalMicroorganismsen_US
dc.source.volume8
dc.source.issue12
refterms.dateFOA2021-01-13T15:12:50Z
dc.source.journaltitleMicroorganisms
dc.source.countrySwitzerland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International