Matches in SemOpenAlex for { <https://semopenalex.org/work/W3088837322> ?p ?o ?g. }
- W3088837322 endingPage "16677" @default.
- W3088837322 startingPage "16665" @default.
- W3088837322 abstract "Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether-containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC-MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation." @default.
- W3088837322 created "2020-10-01" @default.
- W3088837322 creator A5003657445 @default.
- W3088837322 creator A5004650832 @default.
- W3088837322 creator A5005132300 @default.
- W3088837322 creator A5016612884 @default.
- W3088837322 creator A5024800501 @default.
- W3088837322 creator A5045924226 @default.
- W3088837322 creator A5046873300 @default.
- W3088837322 creator A5062031836 @default.
- W3088837322 creator A5063877753 @default.
- W3088837322 creator A5070495567 @default.
- W3088837322 date "2020-12-01" @default.
- W3088837322 modified "2023-10-06" @default.
- W3088837322 title "Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes" @default.
- W3088837322 cites W1587997563 @default.
- W3088837322 cites W1745490809 @default.
- W3088837322 cites W1976007598 @default.
- W3088837322 cites W1976406843 @default.
- W3088837322 cites W1985710061 @default.
- W3088837322 cites W1998027391 @default.
- W3088837322 cites W2008035557 @default.
- W3088837322 cites W2017512654 @default.
- W3088837322 cites W2032726468 @default.
- W3088837322 cites W2039890551 @default.
- W3088837322 cites W2044608069 @default.
- W3088837322 cites W2045636632 @default.
- W3088837322 cites W2071127741 @default.
- W3088837322 cites W2072062484 @default.
- W3088837322 cites W2072535553 @default.
- W3088837322 cites W2081124607 @default.
- W3088837322 cites W2093094655 @default.
- W3088837322 cites W2104836072 @default.
- W3088837322 cites W2108639180 @default.
- W3088837322 cites W2125637695 @default.
- W3088837322 cites W2252545027 @default.
- W3088837322 cites W2315964119 @default.
- W3088837322 cites W2318521608 @default.
- W3088837322 cites W2324131361 @default.
- W3088837322 cites W2327889579 @default.
- W3088837322 cites W2339786511 @default.
- W3088837322 cites W2361660721 @default.
- W3088837322 cites W2396643508 @default.
- W3088837322 cites W2408992521 @default.
- W3088837322 cites W2471857557 @default.
- W3088837322 cites W2550810016 @default.
- W3088837322 cites W2558965245 @default.
- W3088837322 cites W2586914328 @default.
- W3088837322 cites W2592527354 @default.
- W3088837322 cites W2610225122 @default.
- W3088837322 cites W2621442359 @default.
- W3088837322 cites W2707317548 @default.
- W3088837322 cites W2735730838 @default.
- W3088837322 cites W2745901473 @default.
- W3088837322 cites W2749383241 @default.
- W3088837322 cites W2753698499 @default.
- W3088837322 cites W2755025259 @default.
- W3088837322 cites W2768059482 @default.
- W3088837322 cites W2772398261 @default.
- W3088837322 cites W2777114057 @default.
- W3088837322 cites W2782752191 @default.
- W3088837322 cites W2785422592 @default.
- W3088837322 cites W2800087231 @default.
- W3088837322 cites W2879618324 @default.
- W3088837322 cites W2944229994 @default.
- W3088837322 cites W2955815423 @default.
- W3088837322 cites W2963332926 @default.
- W3088837322 cites W2970916907 @default.
- W3088837322 cites W2975466304 @default.
- W3088837322 cites W2989562929 @default.
- W3088837322 cites W2991191656 @default.
- W3088837322 cites W3005139013 @default.
- W3088837322 cites W3012537307 @default.
- W3088837322 doi "https://doi.org/10.1074/jbc.ra120.015371" @default.
- W3088837322 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8188230" @default.
- W3088837322 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33453902" @default.
- W3088837322 hasPublicationYear "2020" @default.
- W3088837322 type Work @default.
- W3088837322 sameAs 3088837322 @default.
- W3088837322 citedByCount "15" @default.
- W3088837322 countsByYear W30888373222021 @default.
- W3088837322 countsByYear W30888373222022 @default.
- W3088837322 countsByYear W30888373222023 @default.
- W3088837322 crossrefType "journal-article" @default.
- W3088837322 hasAuthorship W3088837322A5003657445 @default.
- W3088837322 hasAuthorship W3088837322A5004650832 @default.
- W3088837322 hasAuthorship W3088837322A5005132300 @default.
- W3088837322 hasAuthorship W3088837322A5016612884 @default.
- W3088837322 hasAuthorship W3088837322A5024800501 @default.
- W3088837322 hasAuthorship W3088837322A5045924226 @default.
- W3088837322 hasAuthorship W3088837322A5046873300 @default.
- W3088837322 hasAuthorship W3088837322A5062031836 @default.
- W3088837322 hasAuthorship W3088837322A5063877753 @default.
- W3088837322 hasAuthorship W3088837322A5070495567 @default.
- W3088837322 hasBestOaLocation W30888373221 @default.
- W3088837322 hasConcept C181199279 @default.
- W3088837322 hasConcept C185592680 @default.
- W3088837322 hasConcept C2779281246 @default.