Non-Heme Monooxygenase ThoJ Catalyzes Thioholgamide β-Hydroxylation.
dc.contributor.author | Sikandar, Asfandyar | |
dc.contributor.author | Lopatniuk, Maria | |
dc.contributor.author | Luzhetskyy, Andriy | |
dc.contributor.author | Koehnke, Jesko | |
dc.date.accessioned | 2020-11-16T10:45:03Z | |
dc.date.available | 2020-11-16T10:45:03Z | |
dc.date.issued | 2020-10-01 | |
dc.identifier.citation | ACS Chem Biol. 2020 Oct 16;15(10):2815-2819. doi: 10.1021/acschembio.0c00637. Epub 2020 Oct 1. | en_US |
dc.identifier.pmid | 32965102 | |
dc.identifier.doi | 10.1021/acschembio.0c00637 | |
dc.identifier.uri | http://hdl.handle.net/10033/622584 | |
dc.description.abstract | Thioviridamide-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.iso | en | en_US |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.title | Non-Heme Monooxygenase ThoJ Catalyzes Thioholgamide β-Hydroxylation. | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 1554-8937 | |
dc.contributor.department | HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. | en_US |
dc.identifier.journal | ACS chemical biology | en_US |
dc.source.volume | 15 | |
dc.source.issue | 10 | |
dc.source.beginpage | 2815 | |
dc.source.endpage | 2819 | |
dc.source.journaltitle | ACS chemical biology | |
dc.source.country | United States |