Global ETD Search
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Showing 1 to 9 of 9 for “"YcaO"”.
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Functional and mechanistic elucidation of peptide backbone thioamidation
YcaO enzymes are best known to catalyze the ATP-dependent peptide backbone activation and subsequent formation of azoline heterocycles. It has been proposed that YcaO enzymes can also install lactamidines and thioamides onto peptides through similar mechanisms. These modifications are found in a …
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Elucidation and control of substrate recognition during RiPP biosynthesis
… The catalytic unit of the cyclodehydratase is a YcaO-family protein which is often accompanied by a partner protein from the E1-like superfamily (depending on the of type cyclodehydratase). Although primarily known for azoline formation, recent work suggests that YcaO proteins can use different …
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Practical applications of genomics to natural product discovery and biosynthesis
… we extend this approach to a different area of YcaO biosynthetic enzymes which are implicated to not perform heterocyclizations at all, but instead appear to utilize this mechanism to induce thioamidation, an uncommon and divergent post-translational modification. Genetic evidence is found which …
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Revealing the molecular details of azoline formation in ribosomal natural product biosynthesis
… first function to the previously uncharacterized YcaO superfamily of proteins. Furthermore, in order to complete my mechanistic investigations of the TOMM synthetase, I developed a novel strategy for generating peptides with site-specific carbonyl oxygen isotope labels (chapter 3). I also …
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Metabolite biosynthetic enzymes: catalysis, substrate specificity and protein engineering
… enzymes is LahD1, a protein belonging to the YcaO family of enzymes. The YcaO family of enzymes have been shown to catalyze the formation of azoles, thioamides and amidines but the role of LahD1 is still unknown. In efforts to identify its activity I was able to get the crystal structure of …
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Biochemical and structural studies on proteins involved in the production of natural products and degradation of polysaccharides
… crystallization of the putative cyclodehydratase YcaO. My structural study of YcaO allowed for the identification and characterization of new ATP binding motif present in this family of enzymes. Head to tail macrocyclization is a second type of cyclization observed in serveral RiPP classes …
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Investigating and engineering the post-translational modifications in RiPP natural product biosynthesis (I) Thiopeptides (II) Sactipeptides
… been recently shown to be carried out by TfuA/YcaO enzyme pairs in methanogenic archea. Using TfuA/YcaO as a marker, we discovered an additional thiopeptide featuring thioamidation (saalfelduracin), and associated the previously-orphaned two thioamidated thiopeptides with biosynthetic gene …
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Post-translational modifications catalyzed by RiPP and RiPP-adjacent enzymes
… with a previously misannotated function, EcYcaO, as the catalyst responsible for thioamidation of uL16. We further assess the EcuL16-EcYcaO interaction through site-directed mutagenesis, in vitro reconstitution, and comprehensive computational modeling, unveiling an elaborate protein-protein …
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Post-translational modifications of methyl-coenzyme m reductase in methanosarcina acetivorans
… thioglycine despite the presence of homologs of ycaO and tfuA, the genes required for the synthesis of thioglycine. Finally, in Chapter 4 I summarize all my findings throughout the previous chapters and outline future endeavors that will help in the effort of discovering the identity of the genes …