Show simple item record

dc.contributor.authorGroß, Sebastian
dc.contributor.authorSchnell, Bastien
dc.contributor.authorHaack, Patrick A
dc.contributor.authorAuerbach, David
dc.contributor.authorMüller, Rolf
dc.date.accessioned2021-05-05T14:37:52Z
dc.date.available2021-05-05T14:37:52Z
dc.date.issued2021-03-16
dc.identifier.citationNat Commun. 2021 Mar 16;12(1):1696. doi: 10.1038/s41467-021-21848-3.en_US
dc.identifier.pmid33727542
dc.identifier.doi10.1038/s41467-021-21848-3
dc.identifier.urihttp://hdl.handle.net/10033/622858
dc.description.abstractCystobactamids are myxobacteria-derived topoisomerase inhibitors with potent anti-Gram-negative activity. They are formed by a non-ribosomal peptide synthetase (NRPS) and consist of tailored para-aminobenzoic acids, connected by a unique α-methoxy-L-isoasparagine or a β-methoxy-L-asparagine linker moiety. We describe the heterologous expression of the cystobactamid biosynthetic gene cluster (BGC) in Myxococcus xanthus. Targeted gene deletions produce several unnatural cystobactamids. Using in vitro experiments, we reconstitute the key biosynthetic steps of linker formation and shuttling via CysB to the NRPS. The biosynthetic logic involves a previously uncharacterized bifunctional domain found in the stand-alone NRPS module CysH, albicidin biosynthesis and numerous BGCs of unknown natural products. This domain performs either an aminomutase (AM) or an amide dehydratase (DH) type of reaction, depending on the activity of CysJ which hydroxylates CysH-bound L-asparagine. Furthermore, CysQ O-methylates hydroxyl-L-(iso)asparagine only in the presence of the AMDH domain. Taken together, these findings provide direct evidence for unique steps in cystobactamid biosynthesis.en_US
dc.language.isoenen_US
dc.publisherNature Researchen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleIn vivo and in vitro reconstitution of unique key steps in cystobactamid antibiotic biosynthesis.en_US
dc.typeArticleen_US
dc.identifier.eissn2041-1723
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalNature communicationsen_US
dc.source.volume12
dc.source.issue1
dc.source.beginpage1696
dc.source.endpage
refterms.dateFOA2021-05-05T14:37:52Z
dc.source.journaltitleNature communications
dc.source.countryEngland


Files in this item

Thumbnail
Name:
Groß et al.pdf
Size:
1.703Mb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

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