2026-09-21T17:37:06Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/17023 2023-07-10 col_2142_5131 col_2142_14789 com_2142_5130 com_2142_14788 com_2142_8903

van der Donk, Wilfred A. van der Donk, Wilfred A. Katzenellenbogen, John A. Burke, Martin D. Metcalf, William W. Whitteck, John T. 2010-08-31T20:29:38Z 2010-08-31T20:29:38Z 2012-09-07T16:43:37Z 2010-08 2010-08-31T20:29:38Z 2010-08 Natural product phosphonates are used extensively in the clinic as antibacterials and in commercial agriculture as herbicides. In an effort to efficiently discover new natural product phosphonates, a multidisciplinary, collaborative program has been established at the Institute for Genomic Biology at the University of Illinois at Urbana-Champaign to mine genomes for novel phosphonate structures and biosynthetic enzymes. Detailed herein are my contributions to this effort through assigning the structure of dehydrophos and through investigations into the mechanism of hydroxyethylphosphonate dioxygenase. Dehydrophos was discovered as a secondary metabolite of Streptomyces luridus and was shown to have broad spectrum activity against both Gram-negative and Gram-positive bacteria. Chemical synthesis of the originally proposed structure showed it to be inconsistent with the isolated material. Labeling studies with extensive NMR spectroscopic analysis led to reassignment of the structure as a tripeptide containing an aminophosphonate analogue of dehydroalanine. This structure was confirmed through organic synthesis. Hydroxyethylphosphonate dioxygenase (HEPD) catalyzes a biochemically unprecedented carbon-carbon bond cleavage reaction as part of the early steps of phosphinothricin biosynthesis. Characterization of HEPD has shown it to be a non-heme iron dependent dioxygenase that is dependent on only ferrous iron and molecular oxygen for activity. Studies with substrate isotopologues and substrate analogues have given insight into the mechanism and suggest a hydroperoxylation mechanism for the early steps. Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2010-06-02T15:39:25Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Whitteck_John.pdf: 6251792 bytes, checksum: 2d57e8b0977b6dd2eebfd1458162aa06 (MD5) Made available in DSpace on 2010-08-31T20:29:38Z (GMT). No. of bitstreams: 3 Whitteck_John.pdf: 6251792 bytes, checksum: 2d57e8b0977b6dd2eebfd1458162aa06 (MD5) 1_Whitteck_John.pdf: 6251958 bytes, checksum: 3ece4baf0b794cbe4e00472b0f94da03 (MD5) license.txt: 4063 bytes, checksum: 0cf88a36d6a1375413f7a4603568daff (MD5) Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram (wingram2@illinois.edu) on 2010-08-31T20:32:50Z Item is restricted until 2012-08-31T20:32:49Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2012-09-07T16:43:37Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations and Theses - Chemistry (ID: 676) No. of bitstreams: 3 Whitteck_John.pdf: 6251792 bytes, checksum: 2d57e8b0977b6dd2eebfd1458162aa06 (MD5) 1_Whitteck_John.pdf: 6251958 bytes, checksum: 3ece4baf0b794cbe4e00472b0f94da03 (MD5) license.txt: 4063 bytes, checksum: 0cf88a36d6a1375413f7a4603568daff (MD5) Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2012-09-07T16:43:37Z http://hdl.handle.net/2142/17023 en Copyright 2010 John T. Whitteck biosynthesis phosphonate dehydrophos phosphinothricin hydroxyethylphosphonate dioxygenase Investigation of phosphonate biosynthesis: I. Structure of dehydrophos II. Mechanism of hydroxyethylphosphonate dioxygenase Chemistry 1413 Chemistry 0335 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Chemistry -UIUC 10KS0335PHD