Hudson, G.A., Mitchell, D.A., "RiPP antibiotics: biosynthesis and engineering potential." Curr. Opin. Microbiol., 45: 61-69 (2018). doi:https://doi.org/10.1016/j.mib.2018.02.010

Prominent antibiotic RiPP classes are examined from the standpoint of their defining structural features, mode of action, and biosynthetic malleability.


Mahanta, N., Liu, A., Dong, S., Nair, S.K., Mitchell, D.A. "Enzymatic reconstitution of ribosomal peptide backbone thioamidation." Proc. Natl. Acad. Sci. USA, epub ahead of print (2018). doi:https://doi.org/10.1073/pnas.1722324115

YcaO proteins are shown to catalyze regiospecific thioglycine formation in methyl coenzyme M-reductase in an ATP and sulfide dependent manner.


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., 139: 18154-18157 (2017). doi:10.1021/jacs.7b09899

YcaO proteins are demonstrated to biosynthesize the unique lactamidine macrocycle in the antibiotic bottromycin.


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., 139: 18623-18631 (2017). doi:10.1021/jacs.7b10203

Mechanistic enzymology of a novel radical SAM thiazole C-methyltransferase involved in thiomuracin biosynthesis.


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-cycloaddition in thiopeptide antibiotic biosynthesis." Proc. Natl. Acad. Sci. USA, 114: 12928–12933 (2017). doi:10.1073/pnas.1716035114

Biophysical, structural and computational methods are used to gain mechanistic understanding of thiopeptide [4+2] cycloaddition.


Mahanta, N., Hudson, G.A., Mitchell, D.A. "Radical SAM enzymes involved in RiPP biosynthesis." Biochemistry, 56: 5229-5244 (2017). doi:10.1021/acs.biochem.7b00771

Focusing on the past decade, this review covers six distinct reaction types for radical SAM enzymes involved in RiPP biosynthesis.


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, e29218 (2017). doi:10.7554/eLife.29218

YcaO and TfuA are implicated in the thioamidation of methyl-coenzyme M reductase, a key player in the global carbon cycle.


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., 139: 12466-12473 (2017). doi:10.1021/jacs.7b04641

A high-throughput MALDI MS method for monitoring the formation of microbial secondary metabolites.


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., 6: 629-638 (2017). doi:10.1021/acscentsci.7b00141

A “chimeric leader peptide” strategy enables combination of different RiPP enzymes to rationally design novel hybrid posttranslationally modified peptides.


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., 45: W36-41 (web server issue) (2017). doi:10.1093/nar/gkx319

The latest version of antiSMASH, the premier natural products genome-mining tool, is updated with RODEO's RiPP detection algorithms.


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, 18: 985-991 (2017). doi:10.1002/cbic.201700099

Genome mining of pathogens was used to guide enzymatic characterization of new prenyltransferases.


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., 139: 4310–4313 (2017). doi:10.1021/jacs.7b00693

Characterization of the substrate selectivity and regioselectivity of TbtI, a radical SAM methyltransferase that acts upon an unactivated sp2 thiazole carbon.


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., 117: 5389-5456 (2017). doi:10.1021/acs.chemrev.6b00623

A review of all biosynthetic pathways with a YcaO, the rules governing cyclodehydratases, and the possible role of YcaOs in thioamide and amidine formation.


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., 13:470-478 (2017). doi:10.1038/nchembio.2319

Design of a new genome mining tool guides mapping of a RiPP family and discovery of several new antimicrobial natural products.


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., 138: 15157-15166 (2016). doi:10.1021/jacs.6b06848

Development and use of a new probe for reactivity-based screening to discover a novel natural product and its biosynthetic origin.


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., 138: 15511–15514 (2016). doi:10.1021/jacs.6b08987

A study on the substrate specificity and order of modifications in the biosynthesis of thiomuracin.


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., 11: 2232−2243 (2016). doi:10.1021/acschembio.6b00369

Characterization of the synthetase and new natural products from the plantazolicin family.


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., 24: 6276-6290 (2016). doi:10.1016/j.bmc.2016.05.021

Genomics and reactivity-based labeling were used to identify a hygrobafilomycin gene cluster, probe bioactivity, and elucidate structure.


Tietz, J.I.; Mitchell, D.A. "Using genomics for natural product structure elucidation." Curr. Top. Med. Chem., 16:1645-1694 (2016). doi:10.2174/1568026616666151012111439

A review discussing the use of genomic information to discover and elucidate or confirm the structure of novel natural products.


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 membrane." ACS Infect. Dis., 2:207-220 (2016). doi:10.1021/acsinfecdis.5b00115

The scope of bioactivity and action of plantazolicin on the bacteria cell membrane is elucidated.


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., 137:16012-16015 (2015). doi:10.1021/jacs.5b10194

The total enzymatic synthesis of a thiomuracin antibiotic.


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

Description of the crystal structures for two nelfinavir analogs, establishing the absolute configuration and intra- and inter-molecular interactions.


Cox, C.L.; Doroghazi, J.R.; Mitchell, D.A. "The genomic landscape of ribosomal peptides containing thiazole and oxazole heterocycles." BMC Genomics, 16:778 (2015). doi:10.1186/s12864-015-2008-0

A comprehensive mining effort reveals the genomic landscape of linear azol(in)e-containing peptide biosynthetic gene clusters.


Maxson, T.; Mitchell, D.A. "Targeted treatment for bacterial infections: Prospects for pathogen-specific antibiotics coupled with rapid diagnostics." Tetrahedron (Special Issue on Natural Product-Inspired Approaches to Combat Bacteria), 72: 3609-3624 (2016). doi:10.1016/j.tet.2015.09.069

A review discussing the benefits and drawbacks of narrow-spectrum antibiotics and the diagnostics needed to employ them.


Medema, M.H.; et al. "Minimum information about a biosynthetic gene cluster." Nat. Chem. Biol., 11:625-631 (2015). doi:10.1038/nchembio.1890

The MIBIG specification and database provide a community standard for description and annotation of biosynthetic gene clusters.


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., 15:141 (2015). doi:10.1186/s12866-015-0464-y

Newly-identified truncated SLS-like precursor peptides facilitate a greater understanding of SLS structure-activity relationship.


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., 11:564-570 (2015). doi:10.1038/nchembio.1856

A conserved peptide binding domain recruits precursor peptides to enzymes in diverse RiPP biosynthetic pathways.


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., 137:7672-7677 (2015). doi:10.1021/jacs.5b04682

A novel linear azol(in)e-containing peptide biosynthetic protein is shown to be involved in substrate binding and cyclodehydratase activation.


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., 10:1217–1226 (2015). doi:10.1021/cb500843r

An HIV protease inhibitor is repurposed to block the production of the virulence factor streptolysin S from S. pyogenes.


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., 10:1209–1216 (2015). doi:10.1021/cb501042a

Plantazolicin substructures are used to probe methyltransferase activity and antibacterial specificity.


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., 22:241-250 (2015). doi:10.1016/j.chembiol.2014.11.017

An unusual lasso peptide antibiotic is characterized, and genome sequencing predicts biosynthetic potential in an overlooked genus.


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., 10:823-829 (2014). doi:10.1038/nchembio.1608

X-ray structure of a YcaO family member resolves the linear azol(in)e-containing peptide cyclodehydratase ATP-binding pocket and active site.


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. USA USA, 111:12031-12036 (2014). doi:10.1073/pnas.1406418111

An algorithm-based method uses tandem mass spectra for automatic RiPP structure assignment.


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., 9:2014-2022 (2014). doi:10.1021/cb500324n

Bioinformatics-prioritized reactivity-based screening identifies a new thiopeptide antibiotic.


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., 57:5693–5701 (2014). doi:10.1021/jm5004649

Computer-identified inhibitors of undecaprenyl disphosphate synthase, a novel target in cell wall biosynthesis, kill drug-resistant pathogens.


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., 57:3126-3139 (2014). doi:10.1021/jm500131s

Establishment of antibacterial, antifungal, and antimalarial SAR, as well as mammalian cell toxicity, for a panel of M. tuberculosis drug analogs.


Deane, C.D.; Mitchell, D.A. "Lessons learned from the transformation of natural product discovery to a genome-driven endeavor." J. Ind. Microbiol. Biot., 41:315-331 (2014). doi:10.1007/s10295-013-1361-8

A review on "reverse" discovery of natural products, including lessons learned and recommendations for the future of the field.


Melby, J.O.; Li, X.; Mitchell, D.A. "Orchestration of enzymatic processing by thiazole/oxazole-modified microcin dehydrogenases." Biochemistry, 53:413-422 (2014). doi:10.1021/bi401529y

By separating cyclodehydratase and dehydrogenase activity, dehydrogenase promiscuity and selectivity was investigated.


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., 15:5076-5079 (2013). doi:10.1021/ol402444a

PZN truncations were synthesized to study binding requirements of its methyltransferase.


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-methyltransferase involved in plantazolicin biosynthesis." Proc. Natl. Acad. Sci. USA USA, 110:12954-12959 (2013). doi:10.1073/pnas.1306101110

Studies in the biosynthesis of plantazolicin reveal a methyltransferase with unprecedented selectivity for its substrate.


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., 8:1998-2008 (2013). doi:10.1021/cb4003392

Mutagenesis of the PZN precursor highlights the selectivity of its biosynthetic enyzmes.


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., 135:8692-9701 (2013). doi:10.1021/ja4029507

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.


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 subsp. subtilis strain 168," Acta Cryst., F69:77-79 (2013). doi:10.1107/S1744309112049330

Crystals for structural studies of recombinant B. subtilis protein YisP were obtained, allowing insight into isoprenoid biosynthesis in this organism.


Dunbar, K.L.; Mitchell, D.A. "Revealing Nature's synthetic potential through the study of ribosomal natural product biosynthesis." ACS Chem. Biol., 8:473-487 (2013). doi:10.1021/cb3005325

A review focusing on the diverse biological chemistry discovered in the study of ribosomal natural product biosynthetic enzymes.


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. USA USA, 110:123-128 (2013). doi:10.1073/pnas.1219899110

X-ray structures of ten antibacterial compounds reveal binding to the undecaprenyl diphosphate synthase, an essential cell wall biosynthesis enzyme.


Arnison, P., et al. "Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature." Nat. Prod. Rep., 30:108-160 (2013). doi:10.1039/C2NP20085F

A comprehensive review on ribosomal natural products with a systematic naming system presented for the research community.


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. “HIV-1 integrase inhibitor-inspired antibacterials targeting isoprenoid biosynthesis.” ACS Med. Chem. Lett., 3:402-406 (2012). doi:10.1021/ml300038t

Possessing a similar motif to HIV-1 integrase, prenyl transferases UPPS and CrtM are targeted by keto and diketo-acid compounds.


Dunbar, K.L.; Melby, J.O.; Mitchell, D.A. "YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations." Nat. Chem. Biol., 8:569-575 (2012). doi:10.1038/nchembio.944

A biochemically novel mechanism for ATP use is demonstrated in the context of linear azol(in)e-containing peptide cyclodehydratases.


Melby, J.O.; Dunbar, K.L.; Trinh, N.Q.: Mitchell, D.A. "Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase." J. Am. Chem. Soc., 134:5309-5316 (2012). doi:10.1021/ja211675n

The substrate processing of a Bacillus sp. Al Hakam cyclodehydratase was assessed using mass spectrometry and kinetics.


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., 6:1307-1313 (2011). doi:10.1021/cb200339d

The structure of plantazolicin, a B. anthracis-specific antibiotic, is solved by MS and NMR.


Molloy, E.; Cotter, P.D.; Hill, C.; Mitchell, D.A.; Ross, R.P. “Streptolysin S-like virulence factors: the continuing SagA.” Nat. Rev. Microbiol., 9:670-681 (2011). doi:10.1038/nrmicro2624

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.


Pei, J.; Mitchell, D.A.; Dixon, J.E.; Grishin, N.V. "Expansion of type II CAAX proteases reveals evolutionary origin of γ-secretase subunit APH-1." J Mol. Biol., 410:18-26 (2011). doi:10.1016/j.jmb.2011.04.066

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.


Melby, J.O.; Nard, N.J.; Mitchell, D.A. "Thiazole/oxazole-modified microcins: Complex natural products from ribosomal templates." Curr. Op. Chem. Biol., 15:369-378 (2011). doi:10.1016/j.cbpa.2011.02.027

Review of the linear azol(in)e-containing peptide natural product family with an emphasis on the evolution of novel natural products.


Scholz, R.; Molohon, K.J.; Nachtigall, J.; Vater, J.; Markley, A.L.; Sussmuth, R.D.; Mitchell, D.A.; Borriss, R. “Plantazolicin, a novel microcin B17/streptolysin S-like natural product from Bacillus amyloliquefaciens FZB42.” J. Bacteriol., 193:215-224 (2011). doi:10.1128/JB.00784-10

Discovery of plantazolicin, a posttranslationally modified metabolite which shows specific antimicrobial activity.


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. “Clostridiolysin S: a post-translationally modified biotoxin from Clostridium botulinum.” J. Biol. Chem., 285:28220-28228 (2010). doi:10.1074/jbc.M110.118554


Mitchell, D.A.; Ryabov, A.D.; Kundu, S.; Chanda, A,; Collins, T.J. "Oxidation of pinacyanol chloride by H2O2 catalyzed by FeIII complexed to tetraamidomacrocyclic ligand: unusual kinetics and product identification." J. Coord. Chem., 63:2605-2618 (2010). doi:10.1080/00958972.2010.492426


Haft, D.; Basu, M.; Mitchell, D.A. “Expansion of ribosomally produced natural products: a nitrile hydratase- and Nif11-related precursor family.” BMC Biol., 8:70 (2010). doi:10.1186/1741-7007-8-70

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


Mitchell, D.A.; Lee, S.W.; Pence, M.A.; Markley, A.L.; Limm, J.D.; Nizet, V.; Dixon, J.E. “Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S.” J. Biol. Chem., 284:13004-13012 (2009). doi:10.1074/jbc.M900802200

Identification of residues for synthetase binding and cytolytic activity for the streptolysin S precursor peptide.


Ghosh, A.; Mitchell, D.A.; Chanda, A.; Ryabov, A.D.; Popescu, D.L.; Upham, E.; Collins, T.J. “Catalase-peroxidase activity of iron(III)-TAML activators of hydrogen peroxide.” J. Am. Chem. Soc., 130:15116-15126 (2008). doi:10.1021/ja8043689


Lee, S.W.; Mitchell, D.A.; Markley, A.L.; Hensler, M.E.; Gonzalez, D.; Wohlrab, A.; Dorrestein, P.C.; Nizet, V.; Dixon, J.E. “Discovery of a widely distributed toxin biosynthetic gene cluster.” Proc. Natl. Acad. Sci. USA USA, 105: 5879-5884 (2008). doi:10.1073/pnas.0801338105

The in vitro reconstitution of streptolysin S biosynthesis and the bioinformatics-based discovery of the linear azol(in)e-containing peptide natural product family.


Mitchell, D.A.; Morton, S.U.; Fernhoff, N.B.; Marletta, M.A. “Thioredoxin is required for S-nitrosation of procaspase-3 and inhibits apoptosis in Jurkat cells.” Proc. Natl. Acad. Sci. USA USA, 104:11609-11614 (2007). doi:10.1073/pnas.0704898104


Mitchell, D.A., Marletta, M.A., Michel, T. “Effects of S-nitrosation of nitric oxide synthase isoforms.” (Review) Adv. Exp. Biol., Nitric Oxide 1, Ch. 7. Elsevier Publishing


Chahbane, N.; Popescu, D.L.; Mitchell, D.A.; Chanda, A.; Lenoir, D.; Ryabov, A.D.; Schramm, K.W.; Collins, T.J., “Fe(III)-TAML catalyzed green oxidative degradation of the azo dye Orange II by H2O2 and organic peroxides: products, toxicity, kinetics, and mechanisms.” Green Chem., 9:1-10 (2007). doi:10.1039/B604990G


Mitchell, D.A.; Morton, S.U.; Marletta, M.A. “Design and characterization of an active site selective caspase-3 transnitrosating agent.” ACS Chem. Biol., 1:659-665 (2006). doi:10.1021/cb600393x


Erwin, P.A.; Mitchell, D.A.; Sartoretto, J.; Marletta, M.A.; Michel, T. “Subcellular targeting and differential S-nitrosylation of endothelial nitric oxide synthase.” J. Biol. Chem., 281:151-157 (2006). doi:10.1074/jbc.M510421200


Mitchell, D.A.; Marletta, M.A., “Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine.” Nat. Chem. Biol., 1:154-158 (2005). doi:10.1038/nchembio720


Mitchell, D.A.; Erwin, P.A.; Michel, T.; Marletta, M.A., “S-Nitrosation and regulation of inducible nitric oxide synthase.” Biochemistry, 44:4636-4647 (2005). doi:10.1021/bi0474463


Lazo, J.S.; Nemoto, K.; Pestell, K.E.; Cooley, K.; Southwick, E.C.; Mitchell, D.A.; Furey, W.; Gussio, R.; Zaharevitz, D.W.; Joo, B.; Wipf, P., “Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors.” Mol. Pharmacol., 61:720-728 (2002). doi:10.1124/mol.61.4.720