{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/24489"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/24489","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Head-to-head terpene synthases: Mechanism of action and inhibition","abstract":"“Head-to-head” terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. In this work, I used x-ray crystallography, and mutagenesis to study the catalytic mechanism of Staphylococcus aureus dehydrosqualene synthase. Dehydrosqualene synthase (CrtM) is also the first committed enzyme in the biosynthesis of staphyloxanthin, a carotenoid pigment, and a major virulence factor in S. aureus. Inhibitors targeting CrtM and staphyloxanthin biosynthesis are therefore of interest as “anti-virulence” based therapy for treating S. aureus infection. I studied the structure-activity-relationship of phosphonosulfonate and phosphonoacetamide compounds in CrtM inhibition, and I also developed a series of non-phosphonate CrtM inhibitors using rational- and structure-based approaches.","abstract_html":"“Head-to-head” terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. In this work, I used x-ray crystallography, and mutagenesis to study the catalytic mechanism of Staphylococcus aureus dehydrosqualene synthase. Dehydrosqualene synthase (CrtM) is also the first committed enzyme in the biosynthesis of staphyloxanthin, a carotenoid pigment, and a major virulence factor in S. aureus. Inhibitors targeting CrtM and staphyloxanthin biosynthesis are therefore of interest as “anti-virulence” based therapy for treating S. aureus infection. I studied the structure-activity-relationship of phosphonosulfonate and phosphonoacetamide compounds in CrtM inhibition, and I also developed a series of non-phosphonate CrtM inhibitors using rational- and structure-based approaches.","abstract_has_math":false,"creators":["Lin, Fu-Yang"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Computnl Biology","degree_department":null,"school":null,"contributors":["Oldfield, Eric","Gennis, Robert B.","Nair, Satish K.","Mitchell, Douglas A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-25T14:27:33Z","date_published":"2011-05-25T14:27:33Z","updated_at":"2026-07-22T22:25:23Z","subjects":["terpenes","isoprenoids","antibiotics","virulence factor","dehydrosqualene synthase","Dehydrosqualene synthase (CrtM)","squalene synthase (SQS)","drug design","high throughput screening"],"languages":["en"],"rights":["Copyright 2011 Fu-Yang Lin"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/24489","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Oldfield, Eric","Gennis, Robert B.","Nair, Satish K.","Mitchell, Douglas A."]},{"key":"dc:creator","label":"Author","values":["Lin, Fu-Yang"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-25T14:27:33Z","2013-05-26T10:00:19Z","2011-05"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Computnl Biology"]},{"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":["terpenes","isoprenoids","antibiotics","virulence factor","dehydrosqualene synthase","Dehydrosqualene synthase (CrtM)","squalene synthase (SQS)","drug design","high throughput screening"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2011 Fu-Yang Lin"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/24489"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["“Head-to-head” terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. 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