2.50
Hdl Handle:
http://hdl.handle.net/10033/621190
Title:
The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.
Authors:
Fu, Chengzhang; Sikandar, Asfandyar; Donner, Jannik; Zaburannyi, Nestor; Herrmann, Jennifer; Reck, Michael; Wagner-Döbler, Irene; Koehnke, Jesko; Müller, Rolf ( 0000-0002-1042-5665 )
Abstract:
The natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and was originally described as an antibacterial compound. Here we show that carolacton targets FolD, a key enzyme from the folate-dependent C1 metabolism. We characterize the interaction between bacterial FolD and carolacton biophysically, structurally and biochemically. Carolacton binds FolD with nanomolar affinity, and the crystal structure of the FolD-carolacton complex reveals the mode of binding. We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the growth of cancer cell lines. As mitochondrial MTHFD2 is known to be upregulated in cancer cells, it may be possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anti-cancer target.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124Braunschweig, Germany.
Citation:
The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD. 2017, 8 (1):1529 Nat Commun
Journal:
Nature communications
Issue Date:
16-Nov-2017
URI:
http://hdl.handle.net/10033/621190
DOI:
10.1038/s41467-017-01671-5
PubMed ID:
29142318
Type:
Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
publications of the department of microbial natural substances ([HIPS]MINS); collections of the research group microbial communication (KOM)

Full metadata record

DC FieldValue Language
dc.contributor.authorFu, Chengzhangen
dc.contributor.authorSikandar, Asfandyaren
dc.contributor.authorDonner, Janniken
dc.contributor.authorZaburannyi, Nestoren
dc.contributor.authorHerrmann, Jenniferen
dc.contributor.authorReck, Michaelen
dc.contributor.authorWagner-Döbler, Ireneen
dc.contributor.authorKoehnke, Jeskoen
dc.contributor.authorMüller, Rolfen
dc.date.accessioned2017-12-01T10:57:05Z-
dc.date.available2017-12-01T10:57:05Z-
dc.date.issued2017-11-16-
dc.identifier.citationThe natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD. 2017, 8 (1):1529 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid29142318-
dc.identifier.doi10.1038/s41467-017-01671-5-
dc.identifier.urihttp://hdl.handle.net/10033/621190-
dc.description.abstractThe natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and was originally described as an antibacterial compound. Here we show that carolacton targets FolD, a key enzyme from the folate-dependent C1 metabolism. We characterize the interaction between bacterial FolD and carolacton biophysically, structurally and biochemically. Carolacton binds FolD with nanomolar affinity, and the crystal structure of the FolD-carolacton complex reveals the mode of binding. We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the growth of cancer cell lines. As mitochondrial MTHFD2 is known to be upregulated in cancer cells, it may be possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anti-cancer target.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124Braunschweig, Germany.en
dc.identifier.journalNature communicationsen

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