{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/86691"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/86691","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Genetic and Biochemical Analysis of Phosphinothricin Tripeptide Biosynthesis in Streptomyces Viridochromogenes","abstract":"Our investigations led to the discovery of new biosynthetic intermediates and revealed inaccuracies in the previously published pathway. Specifically, this thesis work established that step III of PTT biosynthesis is the reduction of phosphonoacetaldehyde to hydroxyethylphosphonate by PhpC, an alcohol dehydrogenase with a previously unrecognized role in PTT biosynthesis. We also demonstrated that step IV of PTT biosynthesis is the conversion of hydroxyethylphosphonate to hydroxymethylphosphonate in a chemically novel reaction catalyzed by PhpD, a protein with no recognizable homologs in GenBank. We found evidence to suggest that step V of PTT biosynthesis is the oxidation of hydroxymethylphosphonic acid to phosphonoformaldehyde by PhpE, an alcohol dehydrogenase. Phosphonoformaldehyde is likely then converted into the established intermediate phosphonoformate by the aldehyde dehydrogenase PhpJ (step VI). We demonstrated that phosphonoformate is activated by conjugation to CTP in a reaction catalyzed by PhpF that produces the previously undescribed intermediate CMP-5'-phosphonoformate. Finally, we presented evidence to suggest that CMP-5'-phosphonoformate is likely required for the net incorporation of phosphonoformate into carboxyphosphonoenolpyruvate. This body of work has important implications in our understanding of phosphonic acid antibiotic biosynthesis, a group with great therapeutic promise.","abstract_html":"Our investigations led to the discovery of new biosynthetic intermediates and revealed inaccuracies in the previously published pathway. Specifically, this thesis work established that step III of PTT biosynthesis is the reduction of phosphonoacetaldehyde to hydroxyethylphosphonate by PhpC, an alcohol dehydrogenase with a previously unrecognized role in PTT biosynthesis. We also demonstrated that step IV of PTT biosynthesis is the conversion of hydroxyethylphosphonate to hydroxymethylphosphonate in a chemically novel reaction catalyzed by PhpD, a protein with no recognizable homologs in GenBank. We found evidence to suggest that step V of PTT biosynthesis is the oxidation of hydroxymethylphosphonic acid to phosphonoformaldehyde by PhpE, an alcohol dehydrogenase. Phosphonoformaldehyde is likely then converted into the established intermediate phosphonoformate by the aldehyde dehydrogenase PhpJ (step VI). We demonstrated that phosphonoformate is activated by conjugation to CTP in a reaction catalyzed by PhpF that produces the previously undescribed intermediate CMP-5'-phosphonoformate. Finally, we presented evidence to suggest that CMP-5'-phosphonoformate is likely required for the net incorporation of phosphonoformate into carboxyphosphonoenolpyruvate. This body of work has important implications in our understanding of phosphonic acid antibiotic biosynthesis, a group with great therapeutic promise.","abstract_has_math":false,"creators":["Blodgett, Joshua Alan Van Dyke"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Microbiology","degree_department":null,"school":null,"contributors":["Metcalf, William W."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-28T15:17:27Z","date_published":"2015-09-28T15:17:27Z","updated_at":"2026-07-22T22:26:27Z","subjects":["Biology, Microbiology"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3269843"],"render_values":[{"text":"(MiAaPQ)AAI3269843","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/86691","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Metcalf, William W."]},{"key":"dc:creator","label":"Author","values":["Blodgett, Joshua Alan Van Dyke"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-28T15:17:27Z","10000-01-01","2007"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology"]},{"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":["Biology, Microbiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/86691","(MiAaPQ)AAI3269843"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Our investigations led to the discovery of new biosynthetic intermediates and revealed inaccuracies in the previously published pathway. Specifically, this thesis work established that step III of PTT biosynthesis is the reduction of phosphonoacetaldehyde to hydroxyethylphosphonate by PhpC, an alcohol dehydrogenase with a previously unrecognized role in PTT biosynthesis. We also demonstrated that step IV of PTT biosynthesis is the conversion of hydroxyethylphosphonate to hydroxymethylphosphonate in a chemically novel reaction catalyzed by PhpD, a protein with no recognizable homologs in GenBank. We found evidence to suggest that step V of PTT biosynthesis is the oxidation of hydroxymethylphosphonic acid to phosphonoformaldehyde by PhpE, an alcohol dehydrogenase. Phosphonoformaldehyde is likely then converted into the established intermediate phosphonoformate by the aldehyde dehydrogenase PhpJ (step VI). We demonstrated that phosphonoformate is activated by conjugation to CTP in a reaction catalyzed by PhpF that produces the previously undescribed intermediate CMP-5'-phosphonoformate. Finally, we presented evidence to suggest that CMP-5'-phosphonoformate is likely required for the net incorporation of phosphonoformate into carboxyphosphonoenolpyruvate. This body of work has important implications in our understanding of phosphonic acid antibiotic biosynthesis, a group with great therapeutic promise.","Made available in DSpace on 2015-09-28T15:17:27Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3269843.pdf: 4901844 bytes, checksum: 43c2fda1b8c29e87336aba93e4146123 (MD5) Previous issue date: 2007","Embargo set by: Seth Robbins for item 87972 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","198 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007."]},{"key":"dc:title","label":"Title","values":["Genetic and Biochemical Analysis of Phosphinothricin Tripeptide Biosynthesis in Streptomyces Viridochromogenes"]}]}],"canonical_facts":{"dc:contributor":["Metcalf, William W."],"dc:creator":["Blodgett, Joshua Alan Van Dyke"],"dc:date":["2015-09-28T15:17:27Z","10000-01-01","2007"],"dc:description":["Our investigations led to the discovery of new biosynthetic intermediates and revealed inaccuracies in the previously published pathway. Specifically, this thesis work established that step III of PTT biosynthesis is the reduction of phosphonoacetaldehyde to hydroxyethylphosphonate by PhpC, an alcohol dehydrogenase with a previously unrecognized role in PTT biosynthesis. We also demonstrated that step IV of PTT biosynthesis is the conversion of hydroxyethylphosphonate to hydroxymethylphosphonate in a chemically novel reaction catalyzed by PhpD, a protein with no recognizable homologs in GenBank. We found evidence to suggest that step V of PTT biosynthesis is the oxidation of hydroxymethylphosphonic acid to phosphonoformaldehyde by PhpE, an alcohol dehydrogenase. Phosphonoformaldehyde is likely then converted into the established intermediate phosphonoformate by the aldehyde dehydrogenase PhpJ (step VI). We demonstrated that phosphonoformate is activated by conjugation to CTP in a reaction catalyzed by PhpF that produces the previously undescribed intermediate CMP-5'-phosphonoformate. Finally, we presented evidence to suggest that CMP-5'-phosphonoformate is likely required for the net incorporation of phosphonoformate into carboxyphosphonoenolpyruvate. This body of work has important implications in our understanding of phosphonic acid antibiotic biosynthesis, a group with great therapeutic promise.","Made available in DSpace on 2015-09-28T15:17:27Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3269843.pdf: 4901844 bytes, checksum: 43c2fda1b8c29e87336aba93e4146123 (MD5) Previous issue date: 2007","Embargo set by: Seth Robbins for item 87972 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","198 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007."],"dc:identifier":["http://hdl.handle.net/2142/86691","(MiAaPQ)AAI3269843"],"dc:language":["eng"],"dc:subject":["Biology, Microbiology"],"dc:title":["Genetic and Biochemical Analysis of Phosphinothricin Tripeptide Biosynthesis in Streptomyces Viridochromogenes"],"dc:type":["text"],"thesis:degree_discipline":["Microbiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:27Z"}