In vivo and in vitro reconstitution of unique key steps in cystobactamid antibiotic biosynthesis.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
CitationNat Commun. 2021 Mar 16;12(1):1696. doi: 10.1038/s41467-021-21848-3.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
- Engineering Pseudochelin Production in Myxococcus xanthus.
- Authors: Korp J, Winand L, Sester A, Nett M
- Issue date: 2018 Nov 15
- An Orphan MbtH-Like Protein Interacts with Multiple Nonribosomal Peptide Synthetases in Myxococcus xanthus DK1622.
- Authors: Esquilín-Lebrón KJ, Boynton TO, Shimkets LJ, Thomas MG
- Issue date: 2018 Nov 1
- Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B.
- Authors: Ding W, Deng W, Tang M, Zhang Q, Tang G, Bi Y, Liu W
- Issue date: 2010 Jun
- Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity.
- Authors: Baumann S, Herrmann J, Raju R, Steinmetz H, Mohr KI, Hüttel S, Harmrolfs K, Stadler M, Müller R
- Issue date: 2014 Dec 22
- Biosynthesis of Cittilins, Unusual Ribosomally Synthesized and Post-translationally Modified Peptides from <i>Myxococcus xanthus</i>.
- Authors: Hug JJ, Dastbaz J, Adam S, Revermann O, Koehnke J, Krug D, Müller R
- Issue date: 2020 Aug 21