Details
| Original language | English |
|---|---|
| Pages (from-to) | 2286-2292 |
| Number of pages | 7 |
| Journal | CHEMBIOCHEM |
| Volume | 17 |
| Issue number | 23 |
| Early online date | 21 Sept 2016 |
| Publication status | Published - 5 Dec 2016 |
| Externally published | Yes |
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.
Keywords
- biosynthesis, BotP, bottromycin, leucyl-aminopeptidases, RiPPs
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemistry(all)
- Organic Chemistry
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In: CHEMBIOCHEM, Vol. 17, No. 23, 05.12.2016, p. 2286-2292.
Research output: Contribution to journal › Article › Research › 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 -