Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 2286-2292 |
| Seitenumfang | 7 |
| Fachzeitschrift | CHEMBIOCHEM |
| Jahrgang | 17 |
| Ausgabenummer | 23 |
| Frühes Online-Datum | 21 Sept. 2016 |
| Publikationsstatus | Veröffentlicht - 5 Dez. 2016 |
| Extern publiziert | Ja |
Abstract
The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C-terminal “follower” sequence, rather than the canonical N-terminal “leader” sequence. We report herein the structural and biochemical characterization of BotP, a leucyl-aminopeptidase-like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn 2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro- mycin.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularmedizin
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularbiologie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Biochemie
- Chemie (insg.)
- Organische Chemie
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in: CHEMBIOCHEM, Jahrgang 17, Nr. 23, 05.12.2016, S. 2286-2292.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP
AU - Mann, Greg
AU - Huo, Liujie
AU - Adam, Sebastian
AU - Nardone, Brunello
AU - Vendome, Jeremie
AU - Westwood, Nicholas James
AU - Müller, Rolf
AU - Koehnke, Jesko
N1 - Acknowledgements We acknowledge use of the Diamond (beamline I04–1) and SLS (beamline X06DA) synchrotrons. J.K. would like to thank the University of St. Andrews, which is supported by a Wellcome Trust Capital Award (086036), the Deutsche Forschungsgemeinschaft for an Emmy Noether fellowship (KO4116/3–1) and Daniel Sauer, Dr. Hilda Sucipto and Eva Luxenburger for help with the biochemical assays and MS analysis. B.N. would like to thank the European Research Council (339367).
PY - 2016/12/5
Y1 - 2016/12/5
N2 - The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C-terminal “follower” sequence, rather than the canonical N-terminal “leader” sequence. We report herein the structural and biochemical characterization of BotP, a leucyl-aminopeptidase-like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn 2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro- mycin.
AB - The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C-terminal “follower” sequence, rather than the canonical N-terminal “leader” sequence. We report herein the structural and biochemical characterization of BotP, a leucyl-aminopeptidase-like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn 2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro- mycin.
KW - biosynthesis
KW - BotP
KW - bottromycin
KW - leucyl-aminopeptidases
KW - RiPPs
UR - http://www.scopus.com/inward/record.url?scp=84995575932&partnerID=8YFLogxK
U2 - 10.1002/cbic.201600406
DO - 10.1002/cbic.201600406
M3 - Article
VL - 17
SP - 2286
EP - 2292
JO - CHEMBIOCHEM
JF - CHEMBIOCHEM
SN - 1439-4227
IS - 23
ER -