{"id":285,"date":"2024-11-22T17:21:11","date_gmt":"2024-11-22T17:21:11","guid":{"rendered":"https:\/\/lab.prd.vanderbilt.edu\/mitchell-lab\/?page_id=285"},"modified":"2026-04-01T13:12:50","modified_gmt":"2026-04-01T19:12:50","slug":"2020-current-publications","status":"publish","type":"page","link":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/2020-current-publications\/","title":{"rendered":"2020 – Current Publications"},"content":{"rendered":"
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122<\/h3>\n<\/div>\n
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Carter, R.S.; Ramesh, S.; Saad, H.; Mubarik, A.; Mitchell*, D.A. “Discovery of Partner Protein-Dependent Graspetide Biosynthesis” ACS Chem Biol.<\/i>, X<\/strong>: XXX-XXX (2026). doi: 10.1021\/acschembio.5c00957<\/a><\/p>\n<\/div>\n

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Updates to RODEO-based graspetide detection identified >20,000 BGCs. New examples of partner protein-dependent synthetases were investigated, including one with an unusual 5-hydroxyisopeptide moiety.<\/p>\n<\/div>\n<\/div>\n

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121<\/h3>\n<\/div>\n
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Gadgil, M.G.; Dommaraju* S.R.; Liu, X; Battiste, A.J.; Bregman, M.H.; Mitchell*, D.A. “Biosynthesis of Peptidic Thiooxazole Metallophores Installed by Multinuclear Nonheme Iron Enzymes” ACS Chem Biol.<\/i>, X<\/strong>: XXX-XXX (2026). doi: 10.1021\/acschembio.5c00987<\/a><\/p>\n<\/div>\n

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The largest family of MNIOs (multinuclear nonheme iron-dependent oxidative enzymes) was investigated using bioinformatics, structural characterization of the products, bioactivity studies, and in vitro enzyme activity assays.<\/p>\n<\/div>\n<\/div>\n

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120<\/h3>\n<\/div>\n
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Rice, A.J.; Xue, Y.; Liu, A.; Ramesh, S.; Ashiru, O.A.; Sofela, S.O.; Mitchell, D.A. “Backbone thioamidation of a ribosomal subunit protein in Pseudomonadota.” Biochemistry.<\/i>, X<\/strong>: XXX-XXX (2026). doi:10.1021\/acs.biochem.5c00829<\/a><\/p>\n<\/div>\n

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E. coli’s YcaO enzyme was shown to thiaomidate the uL16 subunit protein of the ribosome, expanding the extent of protein modifications by “RiPP” enzymes.<\/p>\n<\/div>\n<\/div>\n

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119<\/h3>\n<\/div>\n
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Cole, C.G.; Zhang, Z.J.; Dommaraju, S.R.; Dong, Q.; Pope, R.L.; Son, S.S.; McSpadden, E.J.; Woodson, C.K.; Lin, H.; Dylla, N.P.; Sidebottom, A.M.; Sundararajan, A.; Mitchell, D.A.; Pamer, E.G. “Lantibiotic-producing bacteria impact microbiome resilience and colonization resistance.” Cell Host Microbe<\/i>, 33<\/strong>: 2100-2114.e6 (2025). doi:10.1016\/j.chom.2025.11.007<\/a><\/p>\n<\/div>\n

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RODEO-assisted mining of clinical metagenomes shows that lanthipeptide-producing microbes can cause prolonged gut dysbiosis and susceptibility to post-antibiotic infections.<\/p>\n<\/div>\n<\/div>\n

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118<\/h3>\n<\/div>\n
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Bregman, M.H.; Cogan, D.P.; Shelton, K.E.; Rice, A.J.; Dommaraju, S.R.; Nair, S.K.; Mitchell, D.A. “Structure-based discovery and definition of RiPP recognition elements.” mSystems<\/i>, 10<\/strong>: e01252-25 (2025). doi:10.1128\/msystems.01252-25<\/a><\/p>\n<\/div>\n

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Improvements to RRE-Finder expands RRE discovery to >90,000 high-confidence RREs. AlphaFold 3 modeling of >8,000 complexes revealed 13 recognition motifs and validated RRE\u2013peptide interactions.<\/p>\n<\/div>\n<\/div>\n

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117<\/h3>\n<\/div>\n
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Nguyen, D.T.; Ramos-Figueroa, J.S.; Vinogradov, A.A.; Goto, Y.; Gadgil, M.G.; Splain, R.A.; Suga, H.; van der Donk, W.A.; Mitchell, D.A. “Aminoacyl-tRNA specificity of a ligase catalyzing non-ribosomal peptide extension.” J. Am. Chem. Soc.<\/i>, 147<\/strong>: 37893-37898 (2025). doi:10.1021\/jacs.5c12610<\/a><\/p>\n<\/div>\n

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The peptide aminoacyl-tRNA ligase BhaBCala<\/sup> was found to recognize both the amino acid and tRNA components of its substrate, revealing key determinants of specificity and guiding efforts to engineer PEARLs for expanded amino acid incorporation.<\/p>\n<\/div>\n<\/div>\n

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116<\/h3>\n<\/div>\n
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Mi, X.; Barrett, S.E.; Mitchell, D.A; Shukla, D. “LassoESM a tailored language model for enhanced lasso peptide property prediction.” Nat. Commun.<\/i>, 16<\/strong>: 8545 (2025). doi:10.1038\/s41467-025-63412-3<\/a><\/p>\n<\/div>\n

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LassoESM, a lasso peptide-tailored language model, enables accurate prediction of cyclase-substrate compatibility and RNA polymerase inhibitory activity, which empowers rational design and discovery of functional lasso peptides.<\/p>\n<\/div>\n<\/div>\n

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115<\/h3>\n<\/div>\n
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Dommaraju, S.R.; Kandy, S.K.; Ren, H.; Luciano, D.P.; Fujiki, S.; Sarlah, D.; Zhao, H.; Chekan, J.R.; Mitchell, D.A. “A versatile enzymatic pathway for modification of peptide C-termini.” ACS Cent. Sci.<\/i>, 11<\/strong>: 2143-2153 (2025). doi:10.1021\/acscentsci.5c01243<\/a><\/p>\n<\/div>\n

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Daptide biosynthetic enzymes convert peptide C-termini to aminoacetone, diaminopropane, dimethylimidazoline, etc. and can install these modifications onto a broad range of substrates.<\/p>\n<\/div>\n<\/div>\n

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114<\/h3>\n<\/div>\n
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Rice, A.J.; Gadgil, M.G.; Bisignano, P.; Stein, R.A.; Mchaourab, H.S.; Mitchell, D.A. “Peptidic tryptophan halogenation by a promiscuous flavin-dependent enzyme.” Angew. Chem. Int. Ed.<\/i>, e202509729 (2025). doi:10.1002\/anie.202509729<\/a><\/p>\n<\/div>\n

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The tryptophan halogenase ChlH was found to exhibit high selectivity on its native substrate, but modify a diverse array of linear peptides, macrocyclic peptides, and even some proteins in vitro.<\/p>\n<\/div>\n<\/div>\n

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113<\/h3>\n<\/div>\n
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Rice, A.J.; Sword, T.T.; Chengan, K.; Mitchell, D.A.; Mouncey, N.J.; Moore, S.J.; Bailey, C.B. “Cell-free synthetic biology for natural product biosynthesis and discovery.” Chem. Soc. Rev.<\/i>, 54<\/strong>: 4314-4352 (2025). doi:10.1039\/D4CS01198H<\/a><\/p>\n<\/div>\n

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A review article discussing cell-free biosynthesis and the multitude of ways in which it can be leveraged for natural product discovery, production, and engineering.<\/p>\n<\/div>\n<\/div>\n

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112<\/h3>\n<\/div>\n
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Zdouc, M.M.; et al. \u201cMIBiG 4.0 advancing biosynthetic gene cluster curation through global collaboration.\u201d Nucleic Acids Res.<\/i>, 53<\/strong>: D678-D690 (2025). doi:10.1093\/nar\/gkae1115<\/a><\/p>\n<\/div>\n

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This latest release of MIBiG describes numerous enhancements to a premier natural products repository, such as expanded annotation, curation, classification, and strong cross-database integration.<\/p>\n<\/div>\n<\/div>\n

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111<\/h3>\n<\/div>\n
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Clark, J.D.; Mi, X.; Mitchell, D.A.; Shukla, D. \u201cSubstrate prediction for RiPP biosynthetic enzymes via masked language modeling and transfer learning.\u201d Digit. Discov.<\/i>, 4<\/strong>: 343-354 (2025). doi:10.1039\/D4DD00170B<\/a><\/p>\n<\/div>\n

Trained language models on RiPP biosynthetic enzyme substrate preferences. Models developed for specific enzymes improved substrate prediction for distinct enzymes from the same biosynthetic pathway.<\/div>\n<\/div>\n
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110<\/h3>\n<\/div>\n
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Barrett, S.E.; Yin, S.; Jordan, P.; Brunson, J.K.; Gordon-Nunez, J.; Costa Machado da Cruz, G.; Rosario, C.; Okada, B.K.; Anderson, K.; Pires, T.A.; Wang, R.; Shukla, D.; Burk, M.J.; Mitchell, D.A. “Substrate interactions guide cyclase engineering and lasso peptide diversification.” Nat. Chem. Biol.<\/i>, 21<\/strong>: 412-419 (2025). doi:10.1038\/s41589-024-01727-w<\/a><\/p>\n<\/div>\n

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Identifies key interactions between lasso cyclases and their core peptides which provides insights on substrate selectivity and cyclase engineering for lasso peptide diversification.<\/p>\n<\/div>\n<\/div>\n

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109<\/h3>\n<\/div>\n
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Barrett, S.E.; Mitchell, D.A. “Advances in lasso peptide discovery, biosynthesis and function.” Trends Genet.<\/i>, 40<\/strong>: 950-968 (2024). doi:10.1016\/j.tig.2024.08.002<\/a><\/p>\n<\/div>\n

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A review discussing the latest advances for lasso peptide discovery and new insights on lasso peptide biosynthesis and biological function.<\/p>\n<\/div>\n<\/div>\n

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108<\/h3>\n<\/div>\n
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Woodard, A.M.; Peccati, F.; Navo, C.D.; Jim\u00e9nez-Os\u00e9s, G.; Mitchell, D.A. “Darobactin substrate engineering and computation show radical stability governs ether versus C-C bond formation.” J. Am. Chem. Soc.<\/i>, 146<\/b>: 14328-14340 (2024). doi:10.1021\/jacs.4c03994<\/a><\/p>\n<\/div>\n

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Investigation of the radical SAM enzyme involved in darobactin biosynthesis. Computational and experimental work provides new insight into darobactin and rSAM catalysis.<\/p>\n<\/div>\n<\/div>\n

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107<\/h3>\n<\/div>\n
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Lee, A.R.; Carter R.S.; Imani, A.S.; Dommaraju, S.R.; Hudson, G.A.; Mitchell, D.A.; Freeman, M.F. “Discovery of borosin catalytic strategies and function through bioinformatic profiling.” ACS Chem. Biol.<\/i>, 19<\/b>: 1116-1124 (2024). doi:10.1021\/acschembio.4c00066<\/a><\/p>\n<\/div>\n

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RODEO was expanded to analyze borosins, facilitating a large-scale analysis of borosins. This analysis led to the discovery of several new aspects of borosin biosynthesis.<\/p>\n<\/div>\n<\/div>\n

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106<\/h3>\n<\/div>\n
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Shi, C.; Patel, V.D.; Mitchell, D.A.; Zhao, H. “Polythiazole-containing hemolytic peptide from Enterococcus caccae.” ChemBioChem<\/i>, 25<\/b>: e202400212 (2024). doi:10.1002\/cbic.202400212<\/a><\/p>\n<\/div>\n

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A streptolysin S-like cytolysin was discovered in Enterococcus allowing for a more detailed structural characterization of an elusive virulence factor.<\/p>\n<\/div>\n<\/div>\n

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105<\/h3>\n<\/div>\n
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Nguyen, D.T.; Zhu, L.; Gray, D.L.; Woods, T.J.; Padhi, C.; Flatt, K.M.; Mitchell, D.A.; van der Donk, W.A. “Biosynthesis of macrocyclic peptides with C-terminal \u03b2-amino-\u03b1-keto acid groups by three different metalloenzymes.” ACS Cent. Sci.<\/i>, 10<\/b>: 1022-1032 (2024). doi:10.1021\/acscentsci.4c00088<\/a><\/p>\n<\/div>\n

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Bioinformatics was utilized to discover a novel RiPP class biosynthesized by distinct metalloenzyme families including MNIO, B12-rSAM, and cytochrome P450.<\/p>\n<\/div>\n<\/div>\n

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104<\/h3>\n<\/div>\n
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Ren, H.; Huang, C.; Pan, Y.; Dommaraju, S.R.; Cui, H.; Li, M.; Gadgil, M.G.; Mitchell, D.A.; Zhao, H. “Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomomal peptides.” Nat. Chem.<\/i>, 16<\/b>: 1320-1329 (2024). doi:10.1038\/s41557-024-01491-3<\/a><\/p>\n<\/div>\n

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Identified a new compound, “lipoavitide,” that is a fatty acid\/RiPP hybrid. Using structural characterization and in vitro reconstitution, a putative biosynthetic pathway was suggested.<\/p>\n<\/div>\n<\/div>\n

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103<\/h3>\n<\/div>\n
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Harris, L.A.; Saad, H.; Shelton, K.E.; Zhu, L.; Guo, X.; Mitchell, D.A. “Tryptophan-centric bioinformatics identifies new lasso peptide modifications.” Biochem.<\/i>, 63<\/b>: 865-879 (2024). doi:10.1021\/acs.biochem.4c00035<\/a><\/p>\n<\/div>\n

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Bioinformatic strategy to discover lasso peptides with new modifications to tryptophan was used to identify and characterize two news groups of lasso peptides.<\/p>\n<\/div>\n<\/div>\n

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102<\/h3>\n<\/div>\n
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Nguyen, D.T.; Mitchell, D.A.; van der Donk, W.A. “Genome mining for new enzyme chemistry.” ACS Catal.<\/i>, 14<\/b>: 4536-4553 (2024). doi:10.1021\/acscatal.3c06322<\/a><\/p>\n<\/div>\n

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A review describing the advances in mining genome for new chemical transformations.<\/p>\n<\/div>\n<\/div>\n

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101<\/h3>\n<\/div>\n
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Fernandez, H.; Kretsch, A.; Kunakom, S.; Kadjo, A.; Mitchell, D.; Eustaquio, A. “High-yield lasso peptide production in a Burkholderia<\/i> bacterial host by plasmid copy number engineering.” ACS Synth. Biol.<\/i>, 13<\/b>: 337-350 (2024). doi:10.1021\/acssynbio.3c00597<\/a><\/p>\n<\/div>\n

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Tuning of plasmid copy number in a Burkholderia isolate was leveraged to produce two new lasso peptides, mycetolassins, in high titers.<\/p>\n<\/div>\n<\/div>\n

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100<\/h3>\n<\/div>\n
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Saad, H.; Majer, T.; Bhattarai, K.; Lampe, S.; Nguyen, D.T.; Kramer, M.; Straetenger, J.; Oesterbelt, H.B.; Mitchell, D.A.; Gross, H. “Bioinformatic-guided discovery of biaryl-linked lasso peptides.” Chem. Sci.<\/i>, 14<\/b>: 13176-13183 (2023). doi:10.1039\/D3SC02380J<\/a><\/p>\n<\/div>\n

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Discovery and structural characterization of two new (C-N) biaryl-tailored lasso peptides modified by P450 enzymes.<\/p>\n<\/div>\n<\/div>\n

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99<\/h3>\n<\/div>\n
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Chadwick, G.L.; Joiner A.M.N.; Ramesh, S.; Mitchell, D.A.; Nayak, D.D. “McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly.” Proc. Natl. Acad. Sci. U.S.A.<\/i>, 120<\/b>: e2302815120 (2023). doi:10.1073\/pnas.2302815120<\/a><\/p>\n<\/div>\n

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CryoEM reveals the role of McrD in the assembly of methyl-coenzyme M reductase, a ubiquitous enzyme in methanogens and key player in the global carbon cycle.<\/p>\n<\/div>\n<\/div>\n

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98<\/h3>\n<\/div>\n
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Ren, H.; Dommaraju, S.R.; Huang, C.; Cui, H.; Pan, Y.; Nesic, M.; Zhu, L.; Sarlah, D.; Mitchell, D.A.; Zhao, H. “Genome mining unveils a class of ribosomal peptides with two amino termini.” Nat. Commun.<\/i>, 14<\/b>: 1624 (2023). doi:10.1038\/s41467-023-37287-1.<\/a><\/p>\n<\/div>\n

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RRE-Finder was used to bioinformatically discover the daptides, new RiPP class featuring two amino termini.<\/p>\n<\/div>\n<\/div>\n

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97<\/h3>\n<\/div>\n
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Precord, T.W.; Ramesh, S.; Dommaraju, S.R.; Harris, L.A.; Kille, B.L.; Mitchell, D.A. “Catalytic site proximity profiling for functional unification of sequence-diverse radical S-adenosylmethionine enzymes.” ACS Bio. Med. Chem. Au<\/i>, 3<\/b>: 240-251 (2023). doi:10.1021\/acsbiomedchemau.2c00085.<\/a><\/p>\n<\/div>\n

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Identification of paraphyletic sactisynthases by profiling of catalytic site proximity residues. A new sactisynthase from S. sparsogenes is reported using this method.<\/p>\n<\/div>\n<\/div>\n

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96<\/h3>\n<\/div>\n
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Kretsch, A.M.; Gadgil, M.G.; DiCaprio, A.J.; Barrett, S.E.; Kille, B.L.; Si, Y.; Zhu, L.; Mitchell, D.A. “Peptidase activation by a leader peptide-bound RiPP recognition element.” Biochem.<\/i>, 62<\/b>: 956-967 (2023). doi:10.1021\/acs.biochem.2c00700<\/a><\/p>\n<\/div>\n

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Bioinformatic and biochemical techniques unraveled the function of RRE domains in lasso peptide biosynthesis.<\/p>\n<\/div>\n<\/div>\n

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95<\/h3>\n<\/div>\n
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Shelton, K.E.; Mitchell, D.A. “Bioinformatic prediction and experimental validation of RiPP recognition elements.” Meth. Enzymol.<\/i>, 679<\/b>: 191-233 (2023). doi:10.1016\/bs.mie.2022.08.050<\/a><\/p>\n<\/div>\n

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A review covering bioinformatic methods to predict RiPP recognition elements (RREs) and experimental methods to confirm the role of RREs as leader peptide binders.<\/p>\n<\/div>\n<\/div>\n

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94<\/h3>\n<\/div>\n
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Rice, A.J.; Pelton, J.M.; Kramer, N.J.; Catlin, D.S.; Nair, S.K.; Pogorelov, T.V.; Mitchell, D.A.; Bowers, A.A. “Enzymatic pyridine aromatization during thiopeptide biosynthesis.” J. Am. Chem. Soc.<\/i>, 144<\/b>: 21116-21124 (2022). doi:10.1021\/jacs.2c07377<\/a><\/p>\n<\/div>\n

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An in-depth mechanistic investigation of the class-defining [4+2] enzyme in thiopeptide and pyritide biosynthesis.<\/p>\n<\/div>\n<\/div>\n

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93<\/h3>\n<\/div>\n
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Ayikpoe, R.S.; Shi, C.; Battiste, A.J.; Eslami, S.M.; Ramesh, S.; Simon, M.A.; Bothwell, I.R.; Lee, H.; Rice, A.J.; Ren, H.; Tian, Q.; Harris, L.A.; Sarksian, R.; Zhu, L.; Frerk, A.M.; Precord, T.W.; van der Donk, W.A.; Mitchell, D.A.; Zhao, H. “A scalable platform to discover antimicrobials of ribosomal origin.” Nat. Commun.<\/i>, 13<\/b>: 6135 (2022). doi:10.1038\/s41467-022-33890-w<\/a><\/p>\n<\/div>\n

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A robotic system was developed to rapidly refactor RiPP BGCs, which were then expressed in E. coli<\/i>. Using this method, three antibacterial RiPPs were discovered.<\/p>\n<\/div>\n<\/div>\n

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92<\/h3>\n<\/div>\n
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Ongpipattanakul, C.; Desormeaux, E.K.; DiCaprio, A.J.; van der Donk, W.A.; Mitchell, D.A.; Nair, S.K. “Mechanism of action of ribosomally synthesized and post-translationally modified peptides.” Chem. Rev.<\/i>, 122<\/b>: 14722-14814 (2022). doi:10.1021\/acs.chemrev.2c00210<\/a><\/p>\n<\/div>\n

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Comprehensive review of the modes of action of bacterial RiPPs.<\/p>\n<\/div>\n<\/div>\n

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91<\/h3>\n<\/div>\n
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Nguyen, D.T.; Le, T.T.; Rice, A.J.; Hudson, G.A.; van der Donk, W.A.; Mitchell, D.A. “Accessing diverse pyridine-based macrocyclic peptides by a two-site recognition pathway.” J. Am. Chem. Soc.<\/i>, 144<\/b>: 11263-11269 (2022). doi:10.1021\/jacs.2c02824<\/a><\/p>\n<\/div>\n

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Characterization of a versatile biosynthetic pathway to generate 14- to 68-membered pyridine-based macrocyclic peptides with diverse structures.<\/p>\n<\/div>\n<\/div>\n

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90<\/h3>\n<\/div>\n
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Harris, L.A.; Mitchell, D.A. “Reactivity-based screening for natural product discovery.” Meth. Enzymol.<\/i>, 665<\/b>: 177-208 (2022). doi:10.1016\/bs.mie.2021.11.018<\/a><\/p>\n<\/div>\n

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A review detailing the use of reactivity-based screening to discover natural products with specific functional groups.<\/p>\n<\/div>\n<\/div>\n

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89<\/h3>\n<\/div>\n
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Oberg, N.; Precord, T.W.; Mitchell, D.A.; Gerlt, J.A. “RadicalSAM.org: a resource to interpret sequence-function space and discover new radical SAM enzyme chemistry.” ACS Bio. Med. Chem. Au<\/i>, 2<\/b>: 22-35 (2022). doi:10.1021\/acsbiomedchemau.1c00048<\/a><\/p>\n<\/div>\n

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RadicalSAM.org, a new web-based genomic enzymology resource, is described, which aims to accelerate the characterization of the rSAM superfamily.<\/p>\n<\/div>\n<\/div>\n

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88<\/h3>\n<\/div>\n
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Ramesh, S.; Guo, X.; DiCaprio, A.J.; De Lio, A.M.; Harris, L.A.; Kille, B.L.; Pogorelov, T.V.; Mitchell, D.A. “Bioinformatics-guided expansion and discovery of graspetides.” ACS Chem. Biol.<\/i>, 16<\/b>: 2787-2797 (2021). doi:10.1021\/acschembio.1c00672<\/a><\/p>\n<\/div>\n

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RODEO’s utility was expanded to cover graspetides, facilitating the most comprehensive bioinformatic analysis of graspetides to date and the discovery of conformational isomers thatisin and iso-thatisin.<\/p>\n<\/div>\n<\/div>\n

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87<\/h3>\n<\/div>\n
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Liu, A.; Krushnamurthy, P.H.; Subramanya, K.S.; Mitchell, D.A.; Mahanta, N. “Enzymatic thioamidation of peptide backbones.” Meth. Enzymol.<\/i>, 656<\/b>: 459-494 (2021). doi:10.1016\/bs.mie.2021.04.010<\/a><\/p>\n<\/div>\n

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A detailed review of methods and precise experimental protocols for investigating peptide backbone thioamidation by YcaO enzymes.<\/p>\n<\/div>\n<\/div>\n

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86<\/h3>\n<\/div>\n
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Guo, X.R.; Zhang, J.; Li, X.; Xiao, E.; Lange, J.; Rienstra, C.; Burke, M.D.; Mitchell, D.A. “Sterol sponge mechanism is conserved for glycosylated polyene macrolides.” ACS Cent. Sci.<\/i>, 7<\/b>: 781-791 (2021). doi:10.1021\/acscentsci.1c00148<\/a><\/p>\n<\/div>\n

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Bioinformatics and a tetrazine-based probe were used to expand the glycosylated polyene macrolide natural product class, allowing the confirmation of a generalized sterol sponge mechanism of action.<\/p>\n<\/div>\n<\/div>\n

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85<\/h3>\n<\/div>\n
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Si, Y.; Kretsch, A.M.; Daigh, L.M.; Burk, M.J.; Mitchell, D.A. “Cell-Free biosynthesis to evaluate lasso peptide formation and enzyme-substrate tolerance.” J. Am. Chem. Soc.<\/i>, 143<\/b>: 5917-5927 (2021). doi:10.1021\/jacs.1c01452<\/a><\/p>\n<\/div>\n

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Cell-free biosynthesis was used to produce known and novel lasso peptides, and to evaluate enzyme-substrate tolerance.<\/p>\n<\/div>\n<\/div>\n

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84<\/h3>\n<\/div>\n
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Liu, A.; Si, Y.; Dong, S.; Mahanta, N.; Penkala, H.N.; Nair, S.K.; Mitchell, D.A. “Functional elucidation of TfuA in peptide backbone thioamidation.” Nat. Chem. Biol.<\/i>, 17<\/b>: 585-592 (2021). doi:10.1038\/s41589-021-00771-0<\/a><\/p>\n<\/div>\n

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Functional revelation of the TfuA protein family and the proteinaceous sulfur donor involved in peptide backbone thioamidation.<\/p>\n<\/div>\n<\/div>\n

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83<\/h3>\n<\/div>\n
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Harris, L.A.; Saint-Vincent, P.M.B.; Guo, X.R.; Hudson, G.A.; DiCaprio, A.J.; Zhu, L.; Mitchell, D.A. “Reactivity-based screening for citrulline-containing natural products reveals a family of bacterial peptidyl arginine deiminases.” ACS Chem. Biol.<\/i>, 15<\/b>: 3167-3175 (2020). doi:10.1021\/acschembio.0c00685<\/a><\/p>\n<\/div>\n

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A combination of a citrulline specific probe and other methods was used to discover the family of bacterial PADs responsible for converting arginine to citrulline in citrulassin biosynthesis.<\/p>\n<\/div>\n<\/div>\n

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82<\/h3>\n<\/div>\n
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Georgiou, M.A.; Dommaraju, S.R.; Guo, X.R.; Mast, D.H.; Mitchell, D.A. “Bioinformatic and reactivity-based discovery of linaridins.” ACS Chem. Biol.<\/i>, 15<\/b>: 2976-2985 (2020). doi:10.1021\/acschembio.0c00620<\/a><\/p>\n<\/div>\n

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RODEO’s utility was expanded to cover all linaridins, this showed a wide diversity in the subclass and lead to the discovery of pegvadin A and B.<\/p>\n<\/div>\n<\/div>\n

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81<\/h3>\n<\/div>\n
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Montalb\u00e1n-L\u00f3pez, M. et al. “New developments in RiPP discovery, enzymology and engineering.” Nat. Prod. Rep.<\/i>, 38<\/b>: 130-239 (2021). doi:10.1039\/D0NP00027B <\/a><\/p>\n<\/div>\n

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An update to Arnison et al. 2013, this review focuses on the advances in the RiPP field from 2013-2020.<\/p>\n<\/div>\n<\/div>\n

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80<\/h3>\n<\/div>\n
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Kloosterman, A.M.; Shelton, K.E.; van Wezel, G.P.; Medema, M.H.; Mitchell, D.A. “RRE-Finder: A genome-mining tool for class-independent RiPP discovery.” mSystems<\/i>, 5<\/b>: e00267-20 (2020). doi:10.1128\/mSystems.00267-20<\/a><\/p>\n<\/div>\n

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The RRE-Finder tool rapidly identifies RiPP recognition elements in gene clusters, facilitating discovery of novel natural products.<\/p>\n<\/div>\n<\/div>\n

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79<\/h3>\n<\/div>\n
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Hudson, G.A.; Hooper, A.R.; DiCaprio, A.J.; Sarlah, D.; Mitchell, D.A. “Structure prediction and synthesis of pyridine-based macrocyclic peptide natural products.” Org. Lett.<\/i>, 23<\/b>: 253\u2013256 (2021). doi:10.1021\/acs.orglett.0c02699<\/a><\/p>\n<\/div>\n

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The product of a biosynthetic gene cluster was structurally predicted, synthesized, and verified by enzyme reconstitution, requiring a reclassification of thiopeptides as a subclass of the pyritides.<\/p>\n<\/div>\n<\/div>\n

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78<\/h3>\n<\/div>\n
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Walker, M.C.; Eslami, S.M.; Hetrick, K.J.; Ackenhusen, S.E.; Mitchell, D.A.; van der Donk, W.A. “Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family.” BMC Genomics<\/i>, 21<\/b>: 387-403 (2020). doi:10.1186\/s12864-020-06785-7<\/a><\/p>\n<\/div>\n

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RODEO’s utility was expanded to covered all lanthipeptides, revealing the hidden size an diversity of this molecular class while also facilitating the discovery of birimositide.<\/p>\n<\/div>\n<\/div>\n

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77<\/h3>\n<\/div>\n
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Nayak, D.D.; Liu, A.; Agrawal, N.; Rodriguez-Carerro, R.; Dong, S.H.; Mitchell, D.A.; Nair, S.K.; Metcalf, W.W. “Functional interactions between posttranslationally modified amino acids of methyl-coenzyme M reductase in Methanosarcina acetivorans<\/i>.” PLoS Biol.<\/i>, 18<\/b>: e3000507 (2020). doi:10.1371\/journal.pbio.3000507<\/a><\/p>\n<\/div>\n

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Characterization of three posttranslational modifications on methyl-coenzyme M reductase reveals their complex interaction, serving to fine-tune the enzyme activity.<\/p>\n<\/div>\n<\/div>\n

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76<\/h3>\n<\/div>\n
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Sieber, S.; Grendelmeier, S.M.; Harris, L.A.; Mitchell, D.A.; Gademann, K. “Microviridin 1777: A toxic chymotrypsin inhibitor discovered by a metabolomic approach.” J. Nat. Prod.<\/i>, 83<\/b>: 438-446 (2020). doi:10.1021\/acs.jnatprod.9b00986<\/a><\/p>\n<\/div>\n

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A novel chymotrypsin inhibitor, microviridin 1777, was structurally characterized and found to be cytotoxic towards the grazer Thamnocephalus platyurus.<\/p>\n<\/div>\n<\/div>\n

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