{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/129669"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/129669","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Genome mining for natural product biosynthesis: Amino acids, nonribosomal peptides, and ribosomal peptides with posttranslational modifications","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","abstract_has_math":false,"creators":["Yu, Yue"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["van der Donk, Wilfred","Zhao, Huimin","Nair, Satish","Mehta, Angad"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-03-24","date_published":"2025-03-24","updated_at":"2026-07-22T22:25:05Z","subjects":["natural product","biosynthesis","enzymes"],"languages":["en","eng"],"rights":["Copyright 2025 Yue Yu"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/129669","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["van der Donk, Wilfred","Zhao, Huimin","Nair, Satish","Mehta, Angad"]},{"key":"dc:creator","label":"Author","values":["Yu, Yue"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-03-24","2025-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"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 Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["natural product","biosynthesis","enzymes"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2025 Yue Yu"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/129669"]}]},{"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 2027-05-01","The student, Yue Yu, accepted the attached license on 2025-03-14 at 10:28.","The student, Yue Yu, submitted this Dissertation for approval on 2025-03-14 at 12:05.","This Dissertation was approved for publication on 2025-03-24 at 11:23.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21677 on 2025-10-19 at 19:52:29","Natural products, secondary metabolites produced by microbial species, have served as privileged drug scaffolds in human medicine. Their complex structures are biosynthesized by enzymes encoded in the microbial genome, often referred to as biosynthetic gene clusters (BGCs). Despite the importance of natural products, many biosynthetic pathways of known natural products and related enzymatic mechanisms remain poorly understood. In addition, advances in genome sequencing have revealed numerous orphan BGCs, where either the structure of the natural product or the function of encoded enzymes cannot be reliably predicted. These unresolved questions in natural product biosynthesis motivated my research to explore genome mining for discovering biosynthetic pathways with novel biosynthetic logic and enzymatic mechanisms. In Chapter 1, I introduce the biosynthetic machinery responsible for three classes of natural products: nonribosomal peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), and single amino acid-derived natural products, termed pearlins. Chapter 2 describes a carrier peptide-mediated biosynthesis of the pearlin 3-thiahomoleucine and the reconstitution of a cobalamin-dependent radical S-adenosylmethionine enzyme that catalyzes C-isopropylation. Chapter 3 details the discovery of the nonribosomal peptide threopeptin and the biochemical study of a novel peptide extension machinery. Chapter 4 demonstrates how genome mining of enzymes annotated as ‘domain of unknown function’ led to the discovery of new post-translational modifications in peptide natural products. Overall, these studies revealed unexpected enzyme functions and novel biosynthetic strategies, providing new insights into natural product biosynthesis and new opportunities for future bioengineering applications in drug development."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Genome mining for natural product biosynthesis: Amino acids, nonribosomal peptides, and ribosomal peptides with posttranslational modifications"]}]}],"canonical_facts":{"dc:contributor":["van der Donk, Wilfred","Zhao, Huimin","Nair, Satish","Mehta, Angad"],"dc:creator":["Yu, Yue"],"dc:date":["2025-03-24","2025-05"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","The student, Yue Yu, accepted the attached license on 2025-03-14 at 10:28.","The student, Yue Yu, submitted this Dissertation for approval on 2025-03-14 at 12:05.","This Dissertation was approved for publication on 2025-03-24 at 11:23.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21677 on 2025-10-19 at 19:52:29","Natural products, secondary metabolites produced by microbial species, have served as privileged drug scaffolds in human medicine. Their complex structures are biosynthesized by enzymes encoded in the microbial genome, often referred to as biosynthetic gene clusters (BGCs). Despite the importance of natural products, many biosynthetic pathways of known natural products and related enzymatic mechanisms remain poorly understood. In addition, advances in genome sequencing have revealed numerous orphan BGCs, where either the structure of the natural product or the function of encoded enzymes cannot be reliably predicted. These unresolved questions in natural product biosynthesis motivated my research to explore genome mining for discovering biosynthetic pathways with novel biosynthetic logic and enzymatic mechanisms. In Chapter 1, I introduce the biosynthetic machinery responsible for three classes of natural products: nonribosomal peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), and single amino acid-derived natural products, termed pearlins. Chapter 2 describes a carrier peptide-mediated biosynthesis of the pearlin 3-thiahomoleucine and the reconstitution of a cobalamin-dependent radical S-adenosylmethionine enzyme that catalyzes C-isopropylation. Chapter 3 details the discovery of the nonribosomal peptide threopeptin and the biochemical study of a novel peptide extension machinery. Chapter 4 demonstrates how genome mining of enzymes annotated as ‘domain of unknown function’ led to the discovery of new post-translational modifications in peptide natural products. Overall, these studies revealed unexpected enzyme functions and novel biosynthetic strategies, providing new insights into natural product biosynthesis and new opportunities for future bioengineering applications in drug development."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/129669"],"dc:language":["en","eng"],"dc:rights":["Copyright 2025 Yue Yu"],"dc:subject":["natural product","biosynthesis","enzymes"],"dc:title":["Genome mining for natural product biosynthesis: Amino acids, nonribosomal peptides, and ribosomal peptides with posttranslational modifications"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:05Z"}