{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/72281"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/72281","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Biosynthetic Studies on Pactamycin","abstract":"Pactamycin (1), a cytotoxic antibiotic produced by Streptomyces pactum, var. pactum, contains several interesting structural features, including a cyclopentanoid ring, which is rare among natural products, a 6-methylsalicylic acid (6-MSA) unit derived from acetate via a polyketide route, and a m-aminoacetophenone unit, which represents the m-C$\\sb7$N unit found in many antibiotics. It was expected that 6-MSA would be an advanced precursor to the corresponding unit on pactamycin, but feeding experiments with 6-methyl (carboxy-$\\sp $C) salicylic acid and methyl 6-methyl (carboxy-$\\sp $C) salicylate failed to show significant incorporation into either pactamycin or its analogue pactamycate. In addition, these precursors were apparently toxic to S. pactum, causing pronounced acidification of the production medium and substantial reduction of pactamycin production.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)","abstract_html":"Pactamycin (1), a cytotoxic antibiotic produced by Streptomyces pactum, var. pactum, contains several interesting structural features, including a cyclopentanoid ring, which is rare among natural products, a 6-methylsalicylic acid (6-MSA) unit derived from acetate via a polyketide route, and a m-aminoacetophenone unit, which represents the m-C$\\sb7$N unit found in many antibiotics. It was expected that 6-MSA would be an advanced precursor to the corresponding unit on pactamycin, but feeding experiments with 6-methyl (carboxy-$\\sp $C) salicylic acid and methyl 6-methyl (carboxy-$\\sp $C) salicylate failed to show significant incorporation into either pactamycin or its analogue pactamycate. In addition, these precursors were apparently toxic to S. pactum, causing pronounced acidification of the production medium and substantial reduction of pactamycin production.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)","abstract_has_math":true,"creators":["Adams, Erik Stuart"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Rinehart, Kenneth L., Jr."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-17T21:29:06Z","date_published":"2014-12-17T21:29:06Z","updated_at":"2026-07-22T22:26:06Z","subjects":["Biology, Microbiology","Chemistry, Organic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI9328955"],"render_values":[{"text":"(UMI)AAI9328955","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/72281","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Rinehart, Kenneth L., Jr."]},{"key":"dc:creator","label":"Author","values":["Adams, Erik Stuart"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-17T21:29:06Z","10000-01-01","1993"]},{"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":["Biology, Microbiology","Chemistry, Organic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/72281","(UMI)AAI9328955"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Pactamycin (1), a cytotoxic antibiotic produced by Streptomyces pactum, var. pactum, contains several interesting structural features, including a cyclopentanoid ring, which is rare among natural products, a 6-methylsalicylic acid (6-MSA) unit derived from acetate via a polyketide route, and a m-aminoacetophenone unit, which represents the m-C$\\sb7$N unit found in many antibiotics. It was expected that 6-MSA would be an advanced precursor to the corresponding unit on pactamycin, but feeding experiments with 6-methyl (carboxy-$\\sp $C) salicylic acid and methyl 6-methyl (carboxy-$\\sp $C) salicylate failed to show significant incorporation into either pactamycin or its analogue pactamycate. In addition, these precursors were apparently toxic to S. pactum, causing pronounced acidification of the production medium and substantial reduction of pactamycin production.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)","From the feeding experiments with methyl 6-methyl (carboxy-$\\sp $C) salicylate, an unexpected glucuronylated metabolite of this precursor, 2-carbomethoxy-3-methylphenyl-$\\beta$- scD-glucopyranosiduronic acid (2), was isolated as the triethylammonium salt, and its structure was proven by synthesis via a Konigs-Knorr route. Although conjugation of toxic substrates with glucuronic acid for purposes of detoxification is common in animals, this apparently represents the first reported instance of this phenomenon in bacteria.","A new pactamycin analogue, 5$\\sp{\\prime\\prime}$-fluoropactamycin, has also been obtained by directed biosynthesis by supplementing the production medium with 3-amino-5-fluorobenzoic acid hydrochloride. The five-step synthesis of this precursor from 4-fluoro-2-nitroaniline is described. Administration of 3-amino-5-methylbenzoic acid hydrochloride, synthesized in an analogous fashion, did not result in production of the corresponding methylpactamycin, but instead inhibited pactamycin production. The bioactivities of 5$\\sp{\\prime\\prime}$-fluoropactamycin and pactamycin by L1210 murine leukemia cell cytoxicity assay and antimicrobial assay versus B. subtilis were compared and showed no appreciable differences.","Made available in DSpace on 2014-12-17T21:29:06Z (GMT). No. of bitstreams: 1 9328955.pdf: 5580840 bytes, checksum: 129fcc74b1f55b68fbe1d11a9a570ca7 (MD5) Previous issue date: 1993","Embargo set by: Seth Robbins for item 72449 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","152 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1993."]},{"key":"dc:title","label":"Title","values":["Biosynthetic Studies on Pactamycin"]}]}],"canonical_facts":{"dc:contributor":["Rinehart, Kenneth L., Jr."],"dc:creator":["Adams, Erik Stuart"],"dc:date":["2014-12-17T21:29:06Z","10000-01-01","1993"],"dc:description":["Pactamycin (1), a cytotoxic antibiotic produced by Streptomyces pactum, var. pactum, contains several interesting structural features, including a cyclopentanoid ring, which is rare among natural products, a 6-methylsalicylic acid (6-MSA) unit derived from acetate via a polyketide route, and a m-aminoacetophenone unit, which represents the m-C$\\sb7$N unit found in many antibiotics. It was expected that 6-MSA would be an advanced precursor to the corresponding unit on pactamycin, but feeding experiments with 6-methyl (carboxy-$\\sp $C) salicylic acid and methyl 6-methyl (carboxy-$\\sp $C) salicylate failed to show significant incorporation into either pactamycin or its analogue pactamycate. In addition, these precursors were apparently toxic to S. pactum, causing pronounced acidification of the production medium and substantial reduction of pactamycin production.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)","From the feeding experiments with methyl 6-methyl (carboxy-$\\sp $C) salicylate, an unexpected glucuronylated metabolite of this precursor, 2-carbomethoxy-3-methylphenyl-$\\beta$- scD-glucopyranosiduronic acid (2), was isolated as the triethylammonium salt, and its structure was proven by synthesis via a Konigs-Knorr route. Although conjugation of toxic substrates with glucuronic acid for purposes of detoxification is common in animals, this apparently represents the first reported instance of this phenomenon in bacteria.","A new pactamycin analogue, 5$\\sp{\\prime\\prime}$-fluoropactamycin, has also been obtained by directed biosynthesis by supplementing the production medium with 3-amino-5-fluorobenzoic acid hydrochloride. The five-step synthesis of this precursor from 4-fluoro-2-nitroaniline is described. Administration of 3-amino-5-methylbenzoic acid hydrochloride, synthesized in an analogous fashion, did not result in production of the corresponding methylpactamycin, but instead inhibited pactamycin production. The bioactivities of 5$\\sp{\\prime\\prime}$-fluoropactamycin and pactamycin by L1210 murine leukemia cell cytoxicity assay and antimicrobial assay versus B. subtilis were compared and showed no appreciable differences.","Made available in DSpace on 2014-12-17T21:29:06Z (GMT). No. of bitstreams: 1 9328955.pdf: 5580840 bytes, checksum: 129fcc74b1f55b68fbe1d11a9a570ca7 (MD5) Previous issue date: 1993","Embargo set by: Seth Robbins for item 72449 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","152 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1993."],"dc:identifier":["http://hdl.handle.net/2142/72281","(UMI)AAI9328955"],"dc:subject":["Biology, Microbiology","Chemistry, Organic"],"dc:title":["Biosynthetic Studies on Pactamycin"],"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":"2026-07-22T22:26:06Z"}