Item type:Thesis, Open Access

Discovery and insight into the unique tailoring of the paeninodin lasso peptide from paenibacillus dendritiformis C454

Thumbnail Image

Files

dsz.pdf (8.02 MB)

Date

2016-08-24

relationships.isAuthorOf

Publisher

Philipps-Universität Marburg
DOI

item.page.supervisor-of-thesis

Abstract

Lasso peptides, such as microcin J25, BI-32169, lariatin and capistruin, are a structurally unique and pharmacologically relevant class of RiPPs (ribosomally synthesized and posttranslationally modified peptides) natural products. Compared with other intensively modified RiPPs, such as lantibiotics, lasso peptides only have a unique knotted topology in which the tail of the peptide is threaded through an N-terminal macrolactam ring and trapped by steric hindrance of bulky side chains stabilizing the entropically disfavored lasso structure. Except for this unusual knot structure, further posttranslational modifications on lasso peptides are very rare. Besides, lasso peptides have so far only been isolated from Proteo- and Actinobacterial sources. In this thesis, the lasso gene cluster from the Firmicute P. dendritiformis was investigated. Paeninodin, a new lasso peptide with an unusual phosphorylation at the side chain of the last serine was discovered by expression of this cluster in a heterologous host. The Paeninodin lasso peptide was isolated from a culture pellet. Mass spectrometric, carboxypeptidase Y assays and IM-MS studies proved paeninodin to be a new representative of lasso peptides. Morever, the biosynthetic pathway of modified lasso peptide was delineated through in vivo and in vitro studies. The kinase turned out to be a novel lasso peptide precursor kinase with wide substrate specificity. These results provide a way for the generation of novel lasso peptide analogs and, thereby, would facilitate lasso peptide engineering in the future.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2016Issued: 2016-08-24
Faculty
Fachbereich Chemie
Language
eng
Data types
DoctoralThesis
Keywords
lasso peptideModifikationPaeninodinPaeninodinmodificationLassopeptid
DFG-subjects
PhosphorylierungBiosyntheseBacillusBio-Produkt
DDC-Numbers
540
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2016.0481
show more
Zhu, Shaozhou: Discovery and insight into the unique tailoring of the paeninodin lasso peptide from paenibacillus dendritiformis C454. : Philipps-Universität Marburg 2016-08-24. DOI: https://doi.org/10.17192/z2016.0481.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright