Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor
Microcin C7 (McC) is a peptide antibiotic modified by a linkage of the terminal isoAsn amide to AMP via a phosphoramidate bond. Post-translational modification on this ribosomally produced heptapeptide precursor is carried out by MccB, which consumes two equivalents of ATP to generate the N-P linkag...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Royal Society of Chemistry
2018
|
| _version_ | 1826266372479385600 |
|---|---|
| author | Dong, S Kulikovsky, A Zukher, I Estrada, P Dubiley, S Severinov, K Nair, S |
| author_facet | Dong, S Kulikovsky, A Zukher, I Estrada, P Dubiley, S Severinov, K Nair, S |
| author_sort | Dong, S |
| collection | OXFORD |
| description | Microcin C7 (McC) is a peptide antibiotic modified by a linkage of the terminal isoAsn amide to AMP via a phosphoramidate bond. Post-translational modification on this ribosomally produced heptapeptide precursor is carried out by MccB, which consumes two equivalents of ATP to generate the N-P linkage. We demonstrate that MccB only efficiently processes the precursor heptapeptide that retains the N-formylated initiator Met (fMet). Binding studies and kinetic measurements evidence the role of the N-formyl moiety. Structural data show that the N-formyl peptide binding results in an ordering of residues in the MccB "crossover loop", which dictates specificity in homologous ubiquitin activating enzymes. The N-formyl peptide exhibits substrate inhibition, and cannot be displaced from MccB by the desformyl counterpart. Such substrate inhibition may be a strategy to avert unwanted McC buildup and avert toxicity in the cytoplasm of producing organisms. |
| first_indexed | 2024-03-06T20:37:55Z |
| format | Journal article |
| id | oxford-uuid:33408ab3-80d4-4096-a472-8384782dc53b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:37:55Z |
| publishDate | 2018 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:33408ab3-80d4-4096-a472-8384782dc53b2022-03-26T13:19:14ZBiosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursorJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:33408ab3-80d4-4096-a472-8384782dc53bEnglishSymplectic Elements at OxfordRoyal Society of Chemistry2018Dong, SKulikovsky, AZukher, IEstrada, PDubiley, SSeverinov, KNair, SMicrocin C7 (McC) is a peptide antibiotic modified by a linkage of the terminal isoAsn amide to AMP via a phosphoramidate bond. Post-translational modification on this ribosomally produced heptapeptide precursor is carried out by MccB, which consumes two equivalents of ATP to generate the N-P linkage. We demonstrate that MccB only efficiently processes the precursor heptapeptide that retains the N-formylated initiator Met (fMet). Binding studies and kinetic measurements evidence the role of the N-formyl moiety. Structural data show that the N-formyl peptide binding results in an ordering of residues in the MccB "crossover loop", which dictates specificity in homologous ubiquitin activating enzymes. The N-formyl peptide exhibits substrate inhibition, and cannot be displaced from MccB by the desformyl counterpart. Such substrate inhibition may be a strategy to avert unwanted McC buildup and avert toxicity in the cytoplasm of producing organisms. |
| spellingShingle | Dong, S Kulikovsky, A Zukher, I Estrada, P Dubiley, S Severinov, K Nair, S Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor |
| title | Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor |
| title_full | Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor |
| title_fullStr | Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor |
| title_full_unstemmed | Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor |
| title_short | Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor |
| title_sort | biosynthesis of the ripp trojan horse nucleotide antibiotic microcin c is directed by the n formyl of the peptide precursor |
| work_keys_str_mv | AT dongs biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor AT kulikovskya biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor AT zukheri biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor AT estradap biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor AT dubileys biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor AT severinovk biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor AT nairs biosynthesisoftheripptrojanhorsenucleotideantibioticmicrocincisdirectedbythenformylofthepeptideprecursor |