{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/124624"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/124624","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Investigation of lanthipeptides and their applications","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","abstract_has_math":false,"creators":["Eslami, Sara Miriam"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["van der Donk, Wilfred A","Metcalf, William W","Zhao, Huimin","Manesis, Anastasia C"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-05","date_published":"2024-05","updated_at":"2026-07-22T22:25:02Z","subjects":["Lanthipeptide","Ribosomally Synthesized And Post-translationally Modified Peptide"],"languages":["en","eng"],"rights":["© 2024 Sara M. Eslami"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/124624","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["van der Donk, Wilfred A","Metcalf, William W","Zhao, Huimin","Manesis, Anastasia C"]},{"key":"dc:creator","label":"Author","values":["Eslami, Sara Miriam"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-05","2024-02-22"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Lanthipeptide","Ribosomally Synthesized And Post-translationally Modified Peptide"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["© 2024 Sara M. Eslami"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/124624"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","The student, Sara Eslami, accepted the attached license on 2024-02-04 at 19:09.","The student, Sara Eslami, submitted this Dissertation for approval on 2024-02-05 at 19:07.","This Dissertation was approved for publication on 2024-02-22 at 15:46.","DSpace SAF Submission Ingestion Package generated from Vireo submission #20213 on 2024-09-16 at 00:48:47","Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a subset of natural products defined by a genetically encoded precursor peptide that is post-translationally modified by class-defining enzymes. While bioactivity-guided screening remains a popular tool for identifying antimicrobial RiPPs, advances in bioinformatic technologies have allowed for the rapid expansion of novel RiPPs encoded within growing genome databases. Lanthipeptides are a subset of RiPPs characterized by the dehydration of Ser and Thr amino acids to form dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues, respectively; free thiols of Cys residues then react with these dehydrated amino acids in a Michael-type addition to form (methyl)lanthionine rings yielding a stable, multi-cyclic peptide. Lanthipeptides may have diverse activities e.g. anti-bacterial, anti-fungal, anti-viral, and antiallodynic activities. Chapter 2 focuses on the bioinformatics-informed detection and purification of a two-component class II lanthipeptide termed birimositide from the producing organism Streptomyces rimosus subsp. rimosus. The proposed structure of birimositide is illustrated as well as its synergistic antibacterial activity. Chapter 3 demonstrates the utility of bioinformatic tools in generating a high-throughput catalogue of bioactive RiPPs. This effort, termed FAST-RiPPs (fully automated, scalable high-throughput RiPPs), enabled the discovery of novel class III lanthipeptides from undermined phyla. Unique proteases not previously reported in class III biosynthesis are described as well as bioactivity of a class III lanthipeptide from Bacillus amyloliquefaciens. Finally, chapter 4 describes the construction of a lanthipeptide expression system in adherent and suspension mammalian cell lines. The helical, class II lanthipeptide cytolysin L (CylLL), CylLL variants, and the class II lanthipeptide haloduracin A2 were expressed fully modified in mammalian cells. Successful targeting of the lanthipeptides to the nucleus is also shown. Subsequent utilization of this expression system is further suggested for screening of a CylLL library to identify helical protein-protein interaction inhibitors."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Investigation of lanthipeptides and their applications"]}]}],"canonical_facts":{"dc:contributor":["van der Donk, Wilfred A","Metcalf, William W","Zhao, Huimin","Manesis, Anastasia C"],"dc:creator":["Eslami, Sara Miriam"],"dc:date":["2024-05","2024-02-22"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","The student, Sara Eslami, accepted the attached license on 2024-02-04 at 19:09.","The student, Sara Eslami, submitted this Dissertation for approval on 2024-02-05 at 19:07.","This Dissertation was approved for publication on 2024-02-22 at 15:46.","DSpace SAF Submission Ingestion Package generated from Vireo submission #20213 on 2024-09-16 at 00:48:47","Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a subset of natural products defined by a genetically encoded precursor peptide that is post-translationally modified by class-defining enzymes. While bioactivity-guided screening remains a popular tool for identifying antimicrobial RiPPs, advances in bioinformatic technologies have allowed for the rapid expansion of novel RiPPs encoded within growing genome databases. Lanthipeptides are a subset of RiPPs characterized by the dehydration of Ser and Thr amino acids to form dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues, respectively; free thiols of Cys residues then react with these dehydrated amino acids in a Michael-type addition to form (methyl)lanthionine rings yielding a stable, multi-cyclic peptide. Lanthipeptides may have diverse activities e.g. anti-bacterial, anti-fungal, anti-viral, and antiallodynic activities. Chapter 2 focuses on the bioinformatics-informed detection and purification of a two-component class II lanthipeptide termed birimositide from the producing organism Streptomyces rimosus subsp. rimosus. The proposed structure of birimositide is illustrated as well as its synergistic antibacterial activity. Chapter 3 demonstrates the utility of bioinformatic tools in generating a high-throughput catalogue of bioactive RiPPs. This effort, termed FAST-RiPPs (fully automated, scalable high-throughput RiPPs), enabled the discovery of novel class III lanthipeptides from undermined phyla. Unique proteases not previously reported in class III biosynthesis are described as well as bioactivity of a class III lanthipeptide from Bacillus amyloliquefaciens. Finally, chapter 4 describes the construction of a lanthipeptide expression system in adherent and suspension mammalian cell lines. The helical, class II lanthipeptide cytolysin L (CylLL), CylLL variants, and the class II lanthipeptide haloduracin A2 were expressed fully modified in mammalian cells. Successful targeting of the lanthipeptides to the nucleus is also shown. Subsequent utilization of this expression system is further suggested for screening of a CylLL library to identify helical protein-protein interaction inhibitors."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/124624"],"dc:language":["en","eng"],"dc:rights":["© 2024 Sara M. Eslami"],"dc:subject":["Lanthipeptide","Ribosomally Synthesized And Post-translationally Modified Peptide"],"dc:title":["Investigation of lanthipeptides and their applications"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:02Z"}