{"id":276,"date":"2024-11-22T17:17:36","date_gmt":"2024-11-22T17:17:36","guid":{"rendered":"https:\/\/lab.prd.vanderbilt.edu\/mitchell-lab\/?page_id=276"},"modified":"2025-10-10T14:06:53","modified_gmt":"2025-10-10T20:06:53","slug":"276-2","status":"publish","type":"page","link":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/276-2\/","title":{"rendered":"2010 – 2019 Publications"},"content":{"rendered":"
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75<\/h3>\n<\/p><\/div>\n
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Precord, T.W.; Mahanta, N.; Mitchell, D.A. “Reconstitution and substrate specificity of the thioether-forming radical S-adenosylmethionine enzyme in freyrasin biosynthesis.” ACS Chem. Biol.<\/i>, 14<\/b>: 1981-1989 (2019). doi:10.1021\/acschembio.9b00457<\/a><\/p><\/div>\n

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Freyrasin, a thioether-containing RiPP from Paenibacillus polymyxa<\/i>, was characterized in vivo and reconstituted in vitro, yielding the first in-depth characterization of a ranthipeptide.<\/p><\/div>\n<\/div>\n

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74<\/h3>\n<\/p><\/div>\n
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Hudson, G.A.; Burkhart, B.J.; DiCaprio, A.J.; Schwalen, C.; Kille, B.; Pogorelov, T.V.; Mitchell, D.A. “Bioinformatic mapping of radical S-adenosylmethionine-dependent ribosomally synthesized and post-translationally modified peptides identifies new C\u03b1, C\u03b2, and C\u03b3-linked thioether-containing peptides.” J. Am. Chem. Soc.<\/i>, 141<\/b>: 8228-8238 (2019). doi:10.1021\/jacs.9b01519<\/a><\/p><\/div>\n

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RODEO 2.0 was utilized to map thioether rSAMs, revealing a novel sactipeptide as well as a new class of non-C\u03b1-linked thioether RiPPs, now termed ranthipeptides, including the enigmatic \u201cSCIFFs.\u201d<\/p><\/div>\n<\/div>\n

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73<\/h3>\n<\/p><\/div>\n
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Dong, S.H.; Liu, A.; Mahanta, N.; Mitchell, D.A.; Nair, S.K. “Mechanistic basis for ribosomal peptide backbone modifications.” ACS Cent. Sci.<\/i>, 5<\/b>: 842-851 (2019). doi:10.1021\/acscentsci.9b00124<\/a><\/p><\/div>\n

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The first crystal structure of a substrate-bound YcaO illuminate mechanistic conservation across all YcaOs.<\/p><\/div>\n<\/div>\n

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72<\/h3>\n<\/p><\/div>\n
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Mahanta, N.; Szantai-Kis, D.M.; Petersson, E.J.; Mitchell, D.A. “Biosynthesis and chemical applications of thioamides.” ACS Chem. Biol.<\/i>, 14<\/b>: 142-163 (2019). doi:10.1021\/acschembio.8b01022<\/a><\/p><\/div>\n

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Both synthetic and biosynthetic mechanisms of thioamide installation are discussed in the context of physiochemical implications of this rare modification.<\/p><\/div>\n<\/div>\n

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71<\/h3>\n<\/p><\/div>\n
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DiCaprio, A.J.; Firouzbakht, A.; Hudson, G.H.; Mitchell, D.A. “Enzymatic reconstitution and biosynthetic investigation of the lasso peptide fusilassin.” J. Am. Chem. Soc.<\/i>, 141<\/b>: 290-297 (2019). doi:10.1021\/jacs.8b09928<\/a><\/p><\/div>\n

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Reconstitution of the fusilassin biosynthetic enzymes allowed unprecedented access to mechanisms governing lasso peptide biosynthesis.<\/p><\/div>\n<\/div>\n

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70<\/h3>\n<\/p><\/div>\n
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Hegemann, J.D.; Schwalen, C.J.; Mitchell, D.A.; van der Donk, W.A. “Elucidation of the roles of conserved residues in the biosynthesis of the lasso peptide paeninodin.” Chem. Commun.<\/i>, 54<\/b>: 9007-9010 (2018). doi:10.1039\/C8CC04411B<\/a><\/p><\/div>\n

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Mutagenesis of critical residues conserved in lasso peptide biosynthesis reveal specific roles in substrate recognition and enzymatic processing.<\/p><\/div>\n<\/div>\n

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69<\/h3>\n<\/p><\/div>\n
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Schwalen, C.J.; Hudson, G.A.; Kille, B.; Mitchell, D.A. “Bioinformatic expansion and discovery of thiopeptide antibiotics.” J. Am. Chem. Soc.<\/i>, 140<\/b>: 9494-9501 (2018). doi:10.1021\/jacs.8b03896<\/a><\/p><\/div>\n

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Large-scale genome mining reveals a wealth of untapped thiopeptide scaffolds which was leveraged to identify the source of thioamides in ribosomal natural products.<\/p><\/div>\n<\/div>\n

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68<\/h3>\n<\/p><\/div>\n
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Hudson, G.A.; Mitchell, D.A. “RiPP antibiotics: biosynthesis and engineering potential.” Curr. Opin. Microbiol.<\/i>, 45<\/b>: 61-69 (2018). doi.org\/10.1016\/j.mib.2018.02.010<\/a><\/p><\/div>\n

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Prominent antibiotic RiPP classes are examined from the standpoint of their defining structural features, mode of action, and biosynthetic malleability.<\/p><\/div>\n<\/div>\n

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67<\/h3>\n<\/p><\/div>\n
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Mahanta, N.; Liu, A.; Dong, S.; Nair, S.K.; Mitchell, D.A. “Enzymatic reconstitution of ribosomal peptide backbone thioamidation.” Proc. Natl. Acad. Sci. U.S.A.<\/i>, 115<\/b>: 3030-3035 (2018). doi.org\/10.1073\/pnas.1722324115<\/a><\/p><\/div>\n

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YcaO proteins are shown to catalyze regiospecific thioglycine formation in methyl coenzyme M-reductase in an ATP and sulfide dependent manner.<\/p><\/div>\n<\/div>\n

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66<\/h3>\n<\/p><\/div>\n
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Schwalen, C.J.; Hudson, G.A.; Kosol, S.; Mahanta, N.; Challis, G.L.; Mitchell, D.A. “In vitro biosynthetic studies of bottromycin expand the enzymatic capabilities of the YcaO superfamily.” J. Am. Chem. Soc.<\/i>, 139<\/b>: 18154-18157 (2017). doi:10.1021\/jacs.7b09899<\/a><\/p><\/div>\n

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YcaO proteins are demonstrated to biosynthesize the unique lactamidine macrocycle in the antibiotic bottromycin.<\/p><\/div>\n<\/div>\n

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65<\/h3>\n<\/p><\/div>\n
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Zhang, Z.; Mahanta, N.; Hudson, G.A.; Mitchell, D.A.; van der Donk, W.A. “Mechanism of a class C radical SAM thiazole methyl transferase.” J. Am. Chem. Soc.<\/i>, 139<\/b>: 18623-18631 (2017). doi:10.1021\/jacs.7b10203<\/a><\/p><\/div>\n

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Mechanistic enzymology of a novel radical SAM thiazole C-methyltransferase involved in thiomuracin biosynthesis.<\/p><\/div>\n<\/div>\n

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64<\/h3>\n<\/p><\/div>\n
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Cogan, D.P.; Hudson, G.A.; Zhang, Z.; Pogorelov, T.V.; van der Donk, W.A.; Mitchell, D.A.; Nair, S.K. “Structural insights into enzymatic [4+2] aza<\/i>-cycloaddition in thiopeptide antibiotic biosynthesis.” Proc. Natl. Acad. Sci. U.S.A.<\/i>, 114<\/b>: 12928-12933 (2017). doi:10.1073\/pnas.1716035114<\/a><\/p><\/div>\n

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Biophysical, structural and computational methods are used to gain mechanistic understanding of thiopeptide [4+2] cycloaddition.<\/p><\/div>\n<\/div>\n

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63<\/h3>\n<\/p><\/div>\n
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Mahanta, N.; Hudson, G.A.; Mitchell, D.A. “Radical SAM enzymes involved in RiPP biosynthesis.” Biochem.<\/i>, 56<\/b>: 5229-5244 (2017). doi:10.1021\/acs.biochem.7b00771<\/a><\/p><\/div>\n

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Focusing on the past decade, this review covers six distinct reaction types for radical SAM enzymes involved in RiPP biosynthesis.<\/p><\/div>\n<\/div>\n

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62<\/h3>\n<\/p><\/div>\n
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Nayak, D.D.; Mahanta, N.; Mitchell, D.A.; Metcalf, W.W. “Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea.” eLife<\/i>, e29218 (2017). doi:10.7554\/eLife.29218<\/a><\/p><\/div>\n

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YcaO and TfuA are implicated in the thioamidation of methyl-coenzyme M reductase, a key player in the global carbon cycle.<\/p><\/div>\n<\/div>\n

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61<\/h3>\n<\/p><\/div>\n
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Si, T.; Li, B.; Comi, T.J.; Wo, Y.; Hu, P.; Wu, Y.; Min, Y.; Mitchell, D.A.; Zhao, H.; Sweedler, J.V. “Profiling of microbial colonies for high-throughput engineering of multi-step enzymatic reactions via optically guided MALDI MS.” J. Am. Chem. Soc.<\/i>, 139<\/b>: 12466-12473 (2017). doi:10.1021\/jacs.7b04641<\/a><\/p><\/div>\n

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A high-throughput MALDI MS method for monitoring the formation of microbial secondary metabolites.<\/p><\/div>\n<\/div>\n

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60<\/h3>\n<\/p><\/div>\n
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Burkhart, B.J.; Kakkar, N.; Hudson, G.A.; van der Donk, W.A.; Mitchell, D.A. “Chimeric leader peptides for the generation of non-natural hybrid RiPP products” ACS Cent. Sci.<\/i>, 6<\/b>: 629-638 (2017). doi:10.1021\/acscentsci.7b00141<\/a><\/p><\/div>\n

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A \u201cchimeric leader peptide\u201d strategy enables combination of different RiPP enzymes to rationally design novel hybrid posttranslationally modified peptides.<\/p><\/div>\n<\/div>\n

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59<\/h3>\n<\/p><\/div>\n
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Blin, K.; Wolf, T.; Chevrette, M.G.; Lu,X.; Schwalen, C.J.; Kautsar, S.A.; Suarez Duran, H.G.; de los Santos, E.L.C.; Kim, H.U.; Nave, M.; Dickschat, J.S.; Mitchell, D.A.; Shelest, E.; Breitling, R.; Takano, E.; Lee, S.Y.; Weber, T.; Medema, M. “antiSMASH 4.0 – improvements in chemistry prediction and gene cluster boundary identification” Nucleic Acids Res.<\/i>, 45<\/b>: W36-41 (2017). doi:10.1093\/nar\/gkx319<\/a><\/p><\/div>\n

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The latest version of antiSMASH, the premier natural products genome-mining tool, is updated with RODEO’s RiPP detection algorithms.<\/p><\/div>\n<\/div>\n

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58<\/h3>\n<\/p><\/div>\n
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Schwalen, C.J.; Feng, X.; Liu, W.; O-Dowd, B.; Ko, T.P.; Shin, C.J.; Guo, R.T.; Mitchell, D.A.; Oldfield, E. “”Head-to-head” prenyl synthases in some pathogenic bacteria.” ChemBioChem<\/i>, 18<\/b>: 985-991 (2017). doi:10.1002\/cbic.201700099<\/a><\/p><\/div>\n

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Genome mining of pathogens was used to guide enzymatic characterization of new prenyltransferases.<\/p><\/div>\n<\/div>\n

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57<\/h3>\n<\/p><\/div>\n
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Mahanta, N.; Zhang, Z.; Hudson, G.A.; van der Donk, W.; Mitchell, D.A. “Reconstitution and substrate specificity of the radical SAM thiazole C-methyltransferase in thiomuracin biosynthesis” J. Am. Chem. Soc.<\/i>, 139<\/b>: 4310\u20134313 (2017). doi:10.1021\/jacs.7b00693<\/a><\/p><\/div>\n

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Characterization of the substrate selectivity and regioselectivity of TbtI, a radical SAM methyltransferase that acts upon an unactivated sp2 thiazole carbon.<\/p><\/div>\n<\/div>\n

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56<\/h3>\n<\/p><\/div>\n
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Burkhart, B.J.; Schwalen, C.J.; Mann, G.; Naismith, J.H.; Mitchell, D.A. “YcaO-dependent posttranslational amide activation: biosynthesis, structure, and function.” Chem. Rev.<\/i>, 117<\/b>: 5389-5456 (2017). doi:10.1021\/acs.chemrev.6b00623<\/a><\/p><\/div>\n

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A review of all biosynthetic pathways with a YcaO, the rules governing cyclodehydratases, and the possible role of YcaOs in thioamide and amidine formation.<\/p><\/div>\n<\/div>\n

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55<\/h3>\n<\/p><\/div>\n
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Tietz, J.I.; Schwalen, C.J.; Patel, P.S.; Maxson, T.; Blair, P.M.; Tai, H.C.; Zakai, U.Z.; Mitchell, D.A. “A new genome mining tool redefines the lasso peptide biosynthetic landscape.” Nat. Chem. Biol.<\/i>, 13<\/b>: 470-478 (2017). doi:10.1038\/nchembio.2319<\/a><\/p><\/div>\n

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Design of a new genome mining tool guides mapping of a RiPP family and discovery of several new antimicrobial natural products.<\/p><\/div>\n<\/div>\n

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54<\/h3>\n<\/p><\/div>\n
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Maxson, T.; Tietz, J.I.; Hudson, G.A.; Guo, X.R.; Tai, H.; Mitchell, D.A. “Targeting reactive carbonyls for identifying natural products and their biosynthetic origins.” J. Am. Chem. Soc.<\/i>, 138<\/b>: 15157-15166 (2016). doi:10.1021\/jacs.6b06848<\/a><\/p><\/div>\n

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Development and use of a new probe for reactivity-based screening to discover a novel natural product and its biosynthetic origin.<\/p><\/div>\n<\/div>\n

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53<\/h3>\n<\/p><\/div>\n
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Zhang, Z.; Hudson, G.A.; Mahanta, N.; Tietz, J.I.; van der Donk, W.A.; Mitchell, D.A. “Biosynthetic timing and substrate specificity for the thiopeptide thiomuracin.” J. Am. Chem. Soc.<\/i>, 138<\/b>: 15511-15514 (2016). doi:10.1021\/jacs.6b08987<\/a><\/p><\/div>\n

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A study on the substrate specificity and order of modifications in the biosynthesis of thiomuracin.<\/p><\/div>\n<\/div>\n

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52<\/h3>\n<\/p><\/div>\n
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Deane, C.D.; Burkhart, B.J.; Blair, P.M.; Tietz, J.I.; Lin, A.; Mitchell, D.A. “In vitro biosynthesis and substrate tolerance of the plantazolicin family of natural products.” ACS Chem. Biol.<\/i>, 11<\/b>: 2232\u22122243 (2016). doi:10.1021\/acschembio.6b00369<\/a><\/p><\/div>\n

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Characterization of the synthetase and new natural products from the plantazolicin family.<\/p><\/div>\n<\/div>\n

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51<\/h3>\n<\/p><\/div>\n
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Molloy, E.M.; Tietz, J.I.; Blair, P.M.; Mitchell, D.A. “Biological characterization of the hygrobafilomycin antibiotic JBIR-100 and bioinformatic insights into the hygrolide family of natural products.” Bioorg. Med. Chem.<\/i>, 24<\/b>: 6276-6290 (2016). doi:10.1016\/j.bmc.2016.05.021<\/a><\/p><\/div>\n

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Genomics and reactivity-based labeling were used to identify a hygrobafilomycin gene cluster, probe bioactivity, and elucidate structure.<\/p><\/div>\n<\/div>\n

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50<\/h3>\n<\/p><\/div>\n
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Tietz, J.I.; Mitchell, D.A. “Using genomics for natural product structure elucidation.” Curr. Top. Med. Chem.<\/i>, 16<\/b>: 1645-1694 (2016). doi:10.2174\/1568026616666151012111439<\/a><\/p><\/div>\n

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A review discussing the use of genomic information to discover and elucidate or confirm the structure of novel natural products.<\/p><\/div>\n<\/div>\n

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49<\/h3>\n<\/p><\/div>\n
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Molohon, K.; Blair, P.; Park, S.; Doroghazi, J.R.; Maxson, T.; Hershfield, J.; Flatt, K.; Schroeder, N.; Ha, T.; Mitchell, D.A. “Plantazolicin is an ultra-narrow spectrum antibiotic that targets the Bacillus anthracis<\/i> membrane.” ACS Infect. Dis.<\/i>, 2<\/b>: 207-220 (2016). doi:10.1021\/acsinfecdis.5b00115<\/a><\/p><\/div>\n

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The scope of bioactivity and action of plantazolicin on the bacteria cell membrane is elucidated.<\/p><\/div>\n<\/div>\n

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48<\/h3>\n<\/p><\/div>\n
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Hudson, G.A.; Zhang, Z.; Tietz, J.I.; Mitchell, D.A.; van der Donk, W.A. “In vitro biosynthesis of the core scaffold of the thiopeptide thiomuracin.” J. Am. Chem. Soc.<\/i>, 137<\/b>: 16012-16015 (2015). doi:10.1021\/jacs.5b10194<\/a><\/p><\/div>\n

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The total enzymatic synthesis of a thiomuracin antibiotic.<\/p><\/div>\n<\/div>\n

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47<\/h3>\n<\/p><\/div>\n
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Maxson, T.; Bertke, J.A.; Gray, D.L.; Mitchell, D.A. “Crystal structure and absolute configuration of (3S<\/i>,4aS<\/i>,8aS<\/i>)-N-tert<\/i>-butyl-2-[(S<\/i>)-3-(2-chloro-4-nitrobenzamido)-2-hydroxy-propyl]decahydroisoquinoline-3-carboxamide and (3S<\/i>,4aS<\/i>,8aS<\/i>)-N-tert<\/i>-butyl-2-{(S<\/i>)-2-[(S<\/i>)-1-(2-chloro-4-nitrobenzoyl)pyrrolidin-2-yl]-2-hydroxyethyl}decahydroisoquinoline-3-carboxamide.” Acta Cryst.<\/i>, E17<\/strong>: 1401-1407 (2015). doi:10.1107\/S2056989015020046<\/a><\/p><\/div>\n

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Description of the crystal structures for two nelfinavir analogs, establishing the absolute configuration and intra- and inter-molecular interactions.<\/p><\/div>\n<\/div>\n

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46<\/h3>\n<\/p><\/div>\n
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Cox, C.L.; Doroghazi, J.R.; Mitchell, D.A. “The genomic landscape of ribosomal peptides containing thiazole and oxazole heterocycles.” BMC Genomics<\/i>, 16<\/b>: 778 (2015). doi:10.1186\/s12864-015-2008-0<\/a><\/p><\/div>\n

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A comprehensive mining effort reveals the genomic landscape of linear azol(in)e-containing peptide biosynthetic gene clusters.<\/p><\/div>\n<\/div>\n

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45<\/h3>\n<\/p><\/div>\n
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Maxson, T.; Mitchell, D.A. “Targeted treatment for bacterial infections: Prospects for pathogen-specific antibiotics coupled with rapid diagnostics.” Tetrahedron<\/i> (Special Issue on Natural Product-Inspired Approaches to Combat Bacteria), 72<\/b>: 3609-3624 (2016). doi:10.1016\/j.tet.2015.09.069<\/a><\/p><\/div>\n

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A review discussing the benefits and drawbacks of narrow-spectrum antibiotics and the diagnostics needed to employ them.<\/p><\/div>\n<\/div>\n

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44<\/h3>\n<\/p><\/div>\n
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Medema, M.H.; et al. “Minimum information about a biosynthetic gene cluster.” Nat. Chem. Biol.<\/i>, 11<\/b>: 625-631 (2015). doi:10.1038\/nchembio.1890<\/a><\/p><\/div>\n

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The MIBIG specification and database provide a community standard for description and annotation of biosynthetic gene clusters.<\/p><\/div>\n<\/div>\n

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43<\/h3>\n<\/p><\/div>\n
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Molloy, E.M.; Casjens, S.R.; Cox, C.L.; Maxson, T.; Ethridge, N.A.; Margos, G.; Fingerle, V.; Mitchell, D.A. “Identification of the minimal cytolytic unit for streptolysin S and an expansion of the toxin family.” BMC Microbiol.<\/i>, 15<\/b>: 141 (2015). doi:10.1186\/s12866-015-0464-y<\/a><\/p><\/div>\n

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Newly-identified truncated SLS-like precursor peptides facilitate a greater understanding of SLS structure-activity relationship.<\/p><\/div>\n<\/div>\n

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42<\/h3>\n<\/p><\/div>\n
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Burkhart, B.J.; Hudson, G.A.; Dunbar, K.L.; Mitchell, D.A. “A prevalent peptide-binding domain guides ribosomal natural product biosynthesis” Nat. Chem. Biol.<\/i>, 11<\/b>: 564-570 (2015). doi:10.1038\/nchembio.1856<\/a><\/p><\/div>\n

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A conserved peptide binding domain recruits precursor peptides to enzymes in diverse RiPP biosynthetic pathways.<\/p><\/div>\n<\/div>\n

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41<\/h3>\n<\/p><\/div>\n
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Dunbar, K.L.; Tietz, J.I.; Cox, C.L.; Burkhart, B.J.; Mitchell, D.A. “Identification of an auxiliary leader peptide-binding protein required for azoline formation in ribosomal natural products” J. Am. Chem. Soc.<\/i>, 137<\/b>: 7672-7677 (2015). doi:10.1021\/jacs.5b04682<\/a><\/p><\/div>\n

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A novel linear azol(in)e-containing peptide biosynthetic protein is shown to be involved in substrate binding and cyclodehydratase activation.<\/p><\/div>\n<\/div>\n

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40<\/h3>\n<\/p><\/div>\n
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Maxson, T.; Deane, C.D.; Molloy, E.M.; Cox, C.L.; Markley, A.L.; Lee, S.W.; Mitchell, D.A. “HIV protease inhibitors block streptolysin S production” ACS Chem. Biol.<\/i>, 10<\/b>: 1217-1226 (2015). doi:10.1021\/cb500843r<\/a><\/p><\/div>\n

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An HIV protease inhibitor is repurposed to block the production of the virulence factor streptolysin S from S. pyogenes<\/i>.<\/p><\/div>\n<\/div>\n

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39<\/h3>\n<\/p><\/div>\n
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Hao, Y.; Blair, P.M.; Sharma, A.; Mitchell, D.A.; Nair, S.K. “Insights into methyltransferase specificity and bioactivity of derivatives of the antibiotic plantazolicin” ACS Chem. Biol.<\/i>, 10<\/b>: 1209\u20131216 (2015). doi:10.1021\/cb501042a<\/a><\/p><\/div>\n

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Plantazolicin substructures are used to probe methyltransferase activity and antibacterial specificity.<\/p><\/div>\n<\/div>\n

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38<\/h3>\n<\/p><\/div>\n
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Metelev, M.; Tietz, J.I.; Melby, J.O.; Blair, P.M.; Zhu, L.; Livnat, I.; Severinov, K.; Mitchell, D.A. “Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual lasso peptide from an understudied halophilic actinomycete” Chem. Biol.<\/i>, 22<\/b>: 241-250 (2015). doi:10.1016\/j.chembiol.2014.11.017<\/a><\/p><\/div>\n

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An unusual lasso peptide antibiotic is characterized, and genome sequencing predicts biosynthetic potential in an overlooked genus.<\/p><\/div>\n<\/div>\n

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37<\/h3>\n<\/p><\/div>\n
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Dunbar, K.L.; Chekan, J.R.; Cox, C.L.; Burkhart, B.J.; Nair, S.K.; Mitchell, D.A. “Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis” Nat. Chem. Biol.<\/i>, 10<\/b>: 823-829 (2014). doi:10.1038\/nchembio.1608<\/a><\/p><\/div>\n

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X-ray structure of a YcaO family member resolves the linear azol(in)e-containing peptide cyclodehydratase ATP-binding pocket and active site.<\/p><\/div>\n<\/div>\n

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36<\/h3>\n<\/p><\/div>\n
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Zhang, Q.; Ortega, M; Shi, Y.; Wang, H.; Melby, J.O.; Tang, W.; Mitchell, D.A.; van der Donk, W.A. “Structural investigation of ribosomally synthesized natural products by hypothetical structure enumeration and evaluation using tandem MS” Proc. Natl. Acad. Sci. U.S.A.<\/i>, 111<\/b>: 12031-12036 (2014). doi:10.1073\/pnas.1406418111<\/a><\/p><\/div>\n

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An algorithm-based method uses tandem mass spectra for automatic RiPP structure assignment.<\/p><\/div>\n<\/div>\n

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35<\/h3>\n<\/p><\/div>\n
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Cox, C.L.; Tietz, J.I.; Sokolowski, K.; Melby, J.O.; Doroghazi, J.R.; Mitchell, D.A. “Nucleophilic 1,4-additions for natural product discovery” ACS Chem. Biol.<\/i>, 9<\/b>: 2014-2022 (2014). doi:10.1021\/cb500324n<\/a><\/p><\/div>\n

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Bioinformatics-prioritized reactivity-based screening identifies a new thiopeptide antibiotic.<\/p><\/div>\n<\/div>\n

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34<\/h3>\n<\/p><\/div>\n
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Sinko, W.; Wang, Y.; Zhu, W.; Zhang, Y.; Feixas, F.; Cox, C.; Mitchell, D.A.; Oldfield, E.; McCammon, J.A. “Undecaprenyl diphosphate synthase inhibitors: antibacterial drug leads” J. Med. Chem.<\/i>, 57<\/b>: 5693-5701 (2014). doi:10.1021\/jm5004649<\/a><\/p><\/div>\n

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Computer-identified inhibitors of undecaprenyl disphosphate synthase, a novel target in cell wall biosynthesis, kill drug-resistant pathogens.<\/p><\/div>\n<\/div>\n

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33<\/h3>\n<\/p><\/div>\n
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Li, K.; Schurig-Briccio, L.A.; Feng, X.; Upadhyay, A.; Pujari, V.; Lechartier, B.; Fontes, F.L.; Yang, H.; Rao, G.; Zhu, W.; Gulati, A.; No, J.H.; Cintra, G.; Bogue, S.; Liu, Y.-L.; Molohon, K.; Orlean, P.; Mitchell, D.A.; Freitas-Junior, L.; Ren, F.; Sun, H.; Jiang, T.; Li, Y.; Guo, R.-T.; Cole, S.T.; Gennis, R.B.; Crick, D.C.; Oldfield, E. “Multitarget drug discovery for tuberculosis and other infectious diseases.” J. Med. Chem.<\/i>, 57<\/b>: 3126-3139 (2014). doi:10.1021\/jm500131s<\/a><\/p><\/div>\n

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Establishment of antibacterial, antifungal, and antimalarial SAR, as well as mammalian cell toxicity, for a panel of M. tuberculosis drug analogs.<\/p><\/div>\n<\/div>\n

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32<\/h3>\n<\/p><\/div>\n
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Deane, C.D.; Mitchell, D.A. “Lessons learned from the transformation of natural product discovery to a genome-driven endeavor.” J. Ind. Microbiol. Biot.<\/i>, 41<\/b>: 315-331 (2014). doi:10.1007\/s10295-013-1361-8<\/a><\/p><\/div>\n

\n

A review on “reverse” discovery of natural products, including lessons learned and recommendations for the future of the field.<\/p><\/div>\n<\/div>\n

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31<\/h3>\n<\/p><\/div>\n
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Melby, J.O.; Li, X.; Mitchell, D.A. “Orchestration of enzymatic processing by thiazole\/oxazole-modified microcin dehydrogenases.” Biochem.<\/i>, 53<\/b>: 413-422 (2014). doi:10.1021\/bi401529y<\/a><\/p><\/div>\n

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By separating cyclodehydratase and dehydrogenase activity, dehydrogenase promiscuity and selectivity was investigated.<\/p><\/div>\n<\/div>\n

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30<\/h3>\n<\/p><\/div>\n
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Sharma, A.; Blair, P.M.; and Mitchell, D.A. “Synthesis of plantazolicin analogues enables dissection of ligand binding interactions of a highly selective methyltransferase.” Org. Lett.<\/i>, 15<\/b>: 5076-5079 (2013). doi:10.1021\/ol402444a<\/a><\/p><\/div>\n

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PZN truncations were synthesized to study binding requirements of its methyltransferase.<\/p><\/div>\n<\/div>\n

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29<\/h3>\n<\/p><\/div>\n
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Lee, J.; Hao, Y.; Blair, P.M.; Melby, J.O.; Agarwal, V.; Burkhart, B.J.; Nair, S.K.; Mitchell, D.A. “Structural and functional insight into an unexpectedly selective N<\/i>-methyltransferase involved in plantazolicin biosynthesis.” Proc. Natl. Acad. Sci. U.S.A.<\/i>, 110<\/b>: 12954-12959 (2013). doi:10.1073\/pnas.1306101110<\/a><\/p><\/div>\n

\n

Studies in the biosynthesis of plantazolicin reveal a methyltransferase with unprecedented selectivity for its substrate.<\/p><\/div>\n<\/div>\n

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28<\/h3>\n<\/p><\/div>\n
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Deane, C.D.; Melby, J.O.; Molohon, K.J.; Susarrey, A.R.; Mitchell, D.A. “Engineering unnatural variants of plantazolicin through codon reprogramming.” ACS Chem. Biol.<\/i>, 8<\/b>: 1998-2008 (2013). doi:10.1021\/cb4003392<\/a><\/p><\/div>\n

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Mutagenesis of the PZN precursor highlights the selectivity of its biosynthetic enyzmes.<\/p><\/div>\n<\/div>\n

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27<\/h3>\n<\/p><\/div>\n
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Dunbar, K.L.; Mitchell, D.A. “Insights into the mechanism of peptide cyclodehydrations achieved through the chemoenzymatic generation of amide derivatives.” J. Am. Chem. Soc.<\/i>, 135<\/b>: 8692-9701 (2013). doi:10.1021\/ja4029507<\/a><\/p><\/div>\n

\n

The linear azol(in)e-containing peptide cyclodehydratase was used to install isotope labels into peptide backbones, and the resultant product was used as a mechanistic probe.<\/p><\/div>\n<\/div>\n

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26<\/h3>\n<\/p><\/div>\n
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Hu, Y.; Jia, S.; Ren, F.; Huang, C.-H.; Ko, T.-P.; Mitchell, D.A.; Guo, R.-T.; Zheng, Y. “Crystallization and preliminary X-ray diffraction of YisP protein from Bacillus subtilis<\/i>subsp. subtilis<\/i> strain 168,” Acta Cryst.<\/i>, F69<\/strong>: 77-79 (2013). doi:10.1107\/S1744309112049330<\/a><\/p><\/div>\n

\n

Crystals for structural studies of recombinant B. subtilis<\/i> protein YisP were obtained, allowing insight into isoprenoid biosynthesis in this organism.<\/p><\/div>\n<\/div>\n

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25<\/h3>\n<\/p><\/div>\n
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Dunbar, K.L.; Mitchell, D.A. “Revealing nature’s synthetic potential through the study of ribosomal natural product biosynthesis.” ACS Chem. Biol.<\/i>, 8<\/b>: 473-487 (2013). doi:10.1021\/cb3005325<\/a><\/p><\/div>\n

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A review focusing on the diverse biological chemistry discovered in the study of ribosomal natural product biosynthetic enzymes.<\/p><\/div>\n<\/div>\n

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24<\/h3>\n<\/p><\/div>\n
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Zhu, W.; Zhang, Y.; Sinko, W.; Hensler, M.E.; Olson, J.; Molohon, K.J.; Lindert, S.; Cao, R.; Li, K.; Wang, K.; Wang, Y.; Liu, Y.-L.; Sankovsky, A.; de Oliveira, C.A.F.; Mitchell, D.A.; Nizet, V.; McCammon, J.A.; Oldfield, E. “Antibacterial drug leads targeting isoprenoid biosynthesis.” Proc. Natl. Acad. Sci. U.S.A.<\/i>, 110<\/b>: 123-128 (2013). doi:10.1073\/pnas.1219899110<\/a><\/p><\/div>\n

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X-ray structures of ten antibacterial compounds reveal binding to the undecaprenyl diphosphate synthase, an essential cell wall biosynthesis enzyme.<\/p><\/div>\n<\/div>\n

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23<\/h3>\n<\/p><\/div>\n
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Arnison, P.; et al. “Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.” Nat. Prod. Rep.<\/i>, 30<\/b>: 108-160 (2013). doi:10.1039\/C2NP20085F<\/a><\/p><\/div>\n

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A comprehensive review on ribosomal natural products with a systematic naming system presented for the research community.<\/p><\/div>\n<\/div>\n

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22<\/h3>\n<\/p><\/div>\n
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Zhang, Y.; Lin, F.-Y.; Li, K.; Zhu, W.; Liu, Y.-L.; Cao, R.; Pang, R.; Lee, E.; Axelson, J.; Hensler, M.; Wang, K.; Molohon, K.J.; Wang, Y.; Mitchell, D.A.; Nizet, V.; Oldfield, V. \u201cHIV-1 integrase inhibitor-inspired antibacterials targeting isoprenoid biosynthesis.\u201d ACS Med. Chem. Lett<\/i>., 3<\/b>: 402-406 (2012). doi:10.1021\/ml300038t<\/a><\/p><\/div>\n

\n

Possessing a similar motif to HIV-1 integrase, prenyl transferases UPPS and CrtM are targeted by keto and diketo-acid compounds.<\/p><\/div>\n<\/div>\n

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21<\/h3>\n<\/p><\/div>\n
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Dunbar, K.L.; Melby, J.O.; Mitchell, D.A. “YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations.” Nat. Chem. Biol.<\/i>, 8<\/b>: 569-575 (2012). doi:10.1038\/nchembio.944<\/a><\/p><\/div>\n

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A biochemically novel mechanism for ATP use is demonstrated in the context of linear azol(in)e-containing peptide cyclodehydratases.<\/p><\/div>\n<\/div>\n

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20<\/h3>\n<\/p><\/div>\n
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Melby, J.O.; Dunbar, K.L.; Trinh, N.Q.: Mitchell, D.A. “Selectivity, directionality, and promiscuity in peptide processing from a Bacillus<\/i> sp. Al Hakam cyclodehydratase.” J. Am. Chem. Soc.<\/i>, 134<\/b>: 5309-5316 (2012). doi:10.1021\/ja211675n<\/a><\/p><\/div>\n

\n

The substrate processing of a Bacillus<\/i> sp. Al Hakam cyclodehydratase was assessed using mass spectrometry and kinetics.<\/p><\/div>\n<\/div>\n

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19<\/h3>\n<\/p><\/div>\n
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Molohon, K.J.; Melby, J.O.; Lee, J.; Evans, B.S.; Dunbar, K.L.; Bumpus, S.B.; Kelleher, N.L.; Mitchell, D.A. “Structure determination and interception of biosynthetic intermediates for the plantazolicin class of highly discriminating antibiotics.” ACS Chem. Biol.<\/i>, 6<\/b>: 1307-1313 (2011). doi:10.1021\/cb200339d<\/a><\/p><\/div>\n

\n

The structure of plantazolicin, a B. anthracis<\/i>-specific antibiotic, is solved by MS and NMR.<\/p><\/div>\n<\/div>\n

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18<\/h3>\n<\/p><\/div>\n
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Molloy, E.; Cotter, P.D.; Hill, C.; Mitchell, D.A.; Ross, R.P. \u201cStreptolysin S-like virulence factors: the continuing SagA.\u201d Nat. Rev. Microbiol.<\/i>, 9<\/b>: 670-681 (2011). doi:10.1038\/nrmicro2624<\/a><\/p><\/div>\n

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Review of the genetics, biochemistry, and biological functions of Streptolysin S, a virulence-associated cytolytic linear azol(in)e-containing peptide produced by Streptococcus pyogenes.<\/p><\/div>\n<\/div>\n

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17<\/h3>\n<\/p><\/div>\n
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Pei, J.; Mitchell, D.A.; Dixon, J.E.; Grishin, N.V. “Expansion of type II CAAX proteases reveals evolutionary origin of \u03b3-secretase subunit APH-1.” J Mol. Biol.<\/i>, 410<\/b>: 18-26 (2011). doi:10.1016\/j.jmb.2011.04.066<\/a><\/p><\/div>\n

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The discovery that the predicted protease within many linear azol(in)e-containing peptide clusters shares ancestry with a seemingly unrelated eukaryotic protease, gamma-secretase.<\/p><\/div>\n<\/div>\n

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16<\/h3>\n<\/p><\/div>\n
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Melby, J.O.; Nard, N.J.; Mitchell, D.A. “Thiazole\/oxazole-modified microcins: Complex natural products from ribosomal templates.” Curr. Op. Chem. Biol.<\/i>, 15<\/b>: 369-378 (2011). doi:10.1016\/j.cbpa.2011.02.027<\/a><\/p><\/div>\n

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Review of the linear azol(in)e-containing peptide natural product family with an emphasis on the evolution of novel natural products.<\/p><\/div>\n<\/div>\n

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15<\/h3>\n<\/p><\/div>\n
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Scholz, R.; Molohon, K.J.; Nachtigall, J.; Vater, J.; Markley, A.L.; Sussmuth, R.D.; Mitchell, D.A.; Borriss, R. \u201cPlantazolicin, a novel microcin B17\/streptolysin S-like natural product from Bacillus amyloliquefaciens<\/i> FZB42.\u201d J. Bacteriol.<\/i>, 193<\/b>: 215-224 (2011). doi:10.1128\/JB.00784-10<\/a><\/p><\/div>\n

\n

Discovery of plantazolicin, a posttranslationally modified metabolite which shows specific antimicrobial activity.<\/p><\/div>\n<\/div>\n

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14<\/h3>\n<\/p><\/div>\n
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Gonzalez, D.J.; Lee, S.W.; Hensler, M.E.; Dahesh, S.; Markley, A.L.; Mitchell, D.A.; Banderia, N.; Nizet, V.; Dixon, J.E.; Dorrestein, P.C. \u201cClostridiolysin S: a post-translationally modified biotoxin from Clostridium botulinum<\/i>.\u201d J. Biol. Chem.<\/i>, 285<\/b>: 28220-28228 (2010). doi:10.1074\/jbc.M110.118554<\/a><\/p><\/div>\n

\n <\/div>\n<\/div>\n
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13<\/h3>\n<\/p><\/div>\n
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Mitchell, D.A.; Ryabov, A.D.; Kundu, S.; Chanda, A,; Collins, T.J. “Oxidation of pinacyanol chloride by H2<\/sub>O2<\/sub> catalyzed by FeIII complexed to tetraamidomacrocyclic ligand: unusual kinetics and product identification.” J. Coord. Chem.<\/i>, 63<\/b> :2605-2618 (2010). doi:10.1080\/00958972.2010.492426<\/a><\/p><\/div>\n

<\/div>\n<\/div>\n
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12<\/h3>\n<\/p><\/div>\n
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Haft, D.; Basu, M.; Mitchell, D.A. “Expansion of ribosomally produced natural products: a nitrile hydratase- and Nif11-related precursor family.” BMC Biol.<\/i>, 8<\/b>: 70 (2010). doi:10.1186\/1741-7007-8-70<\/a><\/p><\/div>\n

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A bioinformatics-based discovery of novel linear azol(in)e-containing peptide natural products with uncharacteristically long leader peptides that derive from known enzymes.<\/p><\/div>\n<\/div>\n

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