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dc.contributor.authorSikandar, Asfandyar
dc.contributor.authorLopatniuk, Maria
dc.contributor.authorLuzhetskyy, Andriy
dc.contributor.authorKoehnke, Jesko
dc.date.accessioned2020-11-16T10:45:03Z
dc.date.available2020-11-16T10:45:03Z
dc.date.issued2020-10-01
dc.identifier.citationACS Chem Biol. 2020 Oct 16;15(10):2815-2819. doi: 10.1021/acschembio.0c00637. Epub 2020 Oct 1.en_US
dc.identifier.pmid32965102
dc.identifier.doi10.1021/acschembio.0c00637
dc.identifier.urihttp://hdl.handle.net/10033/622584
dc.description.abstractThioviridamide-like compounds, including thioholgamides, are ribosomally synthesized and post-translationally modified peptide natural products with potent anticancer cell activity and an unprecedented structure. Very little is known about their biosynthesis, and we were intrigued by the β-hydroxy-N1, N3-dimethylhistidinium moiety found in these compounds. Here we report the construction of a heterologous host capable of producing thioholgamide with a 15-fold increased yield compared to the wild-type strain. A knockout of thoJ, encoding a predicted nonheme monooxygenase, shows that ThoJ is essential for thioholgamide β-hydroxylation. The crystal structure of ThoJ exhibits a typical mono/dioxygenase fold with conserved key active-site residues. Yet, ThoJ possesses a very large substrate binding pocket that appears suitable to receive a cyclic thioholgamide intermediate for hydroxylation. The improved production of the heterologous host will enable the dissection of the individual biosynthetic steps involved in biosynthesis of this exciting RiPP family.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleNon-Heme Monooxygenase ThoJ Catalyzes Thioholgamide β-Hydroxylation.en_US
dc.typeArticleen_US
dc.identifier.eissn1554-8937
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalACS chemical biologyen_US
dc.source.volume15
dc.source.issue10
dc.source.beginpage2815
dc.source.endpage2819
dc.source.journaltitleACS chemical biology
dc.source.countryUnited States


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Attribution-NonCommercial-ShareAlike 4.0 International
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