{"id":2,"date":"2024-07-17T19:01:49","date_gmt":"2024-07-17T19:01:49","guid":{"rendered":"https:\/\/lab.prd.vanderbilt.edu\/mitchell-lab\/?page_id=2"},"modified":"2026-04-08T07:55:51","modified_gmt":"2026-04-08T13:55:51","slug":"index","status":"publish","type":"page","link":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/","title":{"rendered":"Home"},"content":{"rendered":"<h4><strong>From Genes to Molecules<\/strong><\/h4>\n<p style=\"text-align: justify\"><strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-143\" src=\"https:\/\/cdn.vanderbilt.edu\/t2-main\/lab-prd\/wp-content\/uploads\/sites\/224\/2024\/11\/front-pzn.png\" alt=\"Illustration showing the relationship between DNA, protein structure, and a small molecule: a DNA double helix on the left points via an orange arrow to a folded protein ribbon structure on the right, which then points via another arrow to a linear chemical structure at the bottom.\" width=\"250\" height=\"250\" srcset=\"https:\/\/cdn.vanderbilt.edu\/t2-main\/lab-prd\/wp-content\/uploads\/sites\/224\/2024\/11\/front-pzn.png 480w, https:\/\/cdn.vanderbilt.edu\/t2-main\/lab-prd\/wp-content\/uploads\/sites\/224\/2024\/11\/front-pzn-150x150.png 150w, https:\/\/cdn.vanderbilt.edu\/t2-main\/lab-prd\/wp-content\/uploads\/sites\/224\/2024\/11\/front-pzn-300x300.png 300w\" sizes=\"auto, (max-width: 250px) 100vw, 250px\" \/>We are a chemical biology group that focuses on the study of natural products.<\/strong> Natural products are highly evolved and functionally privileged compounds that often display complex chemical structures. These molecules have inspired generations of synthetic organic chemists, unveiled numerous fundamental biological processes as chemical probes, and served as the most significant source of chemical matter for drug discovery.<\/p>\n<p style=\"text-align: justify\">As the field of genomics has expanded, it has revealed a vast untapped wealth of natural products encoded in the DNA of sequenced organisms, particularly bacteria. Our lab has developed new tools to expedite the discovery of natural products from genomic information, including molecules from bacteria that cannot be cultivated in a lab. In particular, our lab focuses on <span style=\"text-decoration: underline\">Ri<\/span>bosomally synthesized and <span style=\"text-decoration: underline\">P<\/span>ost-translationally modified <span style=\"text-decoration: underline\">P<\/span>eptides (<a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC7864896\/\" target=\"_blank\" rel=\"noopener\">RiPPs<\/a>) which have genetically encoded substrates and an incredible diversity of post-translational modifications. Using a genes-to-molecule approach, we have uncovered numerous structurally unique RiPP molecules and revealed the unprecedented mechanistic enzymology through which they form.<\/p>\n<p style=\"text-align: justify\">We can then leverage this knowledge to produce new-to-nature compounds with improved properties or novel activity with the long-term goal of unleashing the full synthetic potential of Nature to reshape the diagnosis and treatment of human disease.<\/p>\n<div class='panel-group VUaccordion' id='accordion' role='tablist' aria-multiselectable='true'>\n<div class=\"panel panel-default\">\n<div class=\"panel-heading\" role=\"tab\" id=\"heading1\">\n<h4 class=\"panel-title\"><a role=\"button\" data-toggle=\"collapse\" data-parent=\"#accordion\" href=\"#item1\" aria-expanded=\"true\" aria-controls=\"item1\"><i class='pull-right fa fa-chevron-circle-down' aria-hidden='true'><\/i>Outsmarting Bacteria Since 2009<\/a><\/h4>\n<\/div>\n<div id=\"item1\" class=\"panel-collapse collapse\" role=\"tabpanel\" aria-labelledby=\"heading1\">\n<div class=\"panel-body\">\n<p>\nEven though bacteria are single-celled organisms that lack nuclei, bacterial pathogens are a formidable opponent to the high and mighty Homo sapiens. In a typical healthy human, bacterial cells can rival human cells in number. These clever organisms live in every conceivable niche on earth, including the ocean floor, underneath Arctic ice, hot springs with boiling acid, and inside volcanoes. Some bacteria can even survive chemical assaults as abrasive as hypochlorite (bleach), povidone-iodine (Betadine, a surgical antiseptic), and the interior of activated macrophages. Hundreds of different types of bacteria have been shown to use commonly prescribed antibiotics as their sole sources of carbon. Moreover, they have adapted innumerable methods to hijack animal, plant, and fungal signal transduction pathways that lead to improved metabolism (you couldn&#8217;t properly digest one bite of food without bacteria) and pathological conditions. Even with modern medicine, poverty and drug resistant strains contribute to approximately 15 million human deaths per year from bacterial infections. This is more than double the entire population of Tennessee! Outsmarting bacteria may seem on the surface to be simple, but will be anything but easy.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<h4><strong>Highlights<\/strong><\/h4>\n\n\n<div id=\"vu-slider\" class=\"vu-slider carousel slide vumedia_927 vu-edgeslider carousel-fade\" data-ride=\"carousel\">\n<div class=\"carousel-control-group-container\">\n        <div class=\"carousel-control-group\">\n        <a class=\"left carousel-control\" href=\"#vu-slider\" role=\"button\" data-slide=\"prev\"><i class=\"fa fa-caret-left\" aria-hidden=\"true\"><\/i><span class=\"sr-only\">Previous<\/span><\/a>\n        <ol class=\"carousel-indicators\"><\/ol>\n        <a class=\"right carousel-control\" href=\"#vu-slider\" role=\"button\" data-slide=\"next\"><i class=\"fa fa-caret-right\" aria-hidden=\"true\"><\/i><span class=\"sr-only\">Next<\/span><\/a>\n        <\/div>\n        <\/div>\n<div class=\"carousel-inner\" role=\"listbox\"><a id=\"vumediaitem_6413\" href=\"https:\/\/https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/6413-20260316125919-Untitleddesign51.png\" alt=\"Andrew and Yanqing, along with past and present members of the lab, have published a paper in ACS Biochemistry identifying the activity of E. coli's YcaO enzyme: thioamidation of ribosomal protein uL16.\" title=\"Andrew and Yanqing, along with past and present members of the lab, have published a paper in ACS Biochemistry identifying the activity of E. coli's YcaO enzyme: thioamidation of ribosomal protein uL16.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6412\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/6412-20260316084847-DiscoveryofPartnerProteinDependentGraspetideBiosynthesis.png\" alt=\"Riley and collaborators from the Mitchell lab published an article in ACS Chemical Biology about the discovery and characterization of several examples of partner protein-dependent graspetide biosynthesis.\" title=\"Riley and collaborators from the Mitchell lab published an article in ACS Chemical Biology about the discovery and characterization of several examples of partner protein-dependent graspetide biosynthesis.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6405\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/927-20260313133551-Biosynthesisofpeptidicthiooxazolemetallophoresinstalledbymultinuclearnonhemeironenzymes.png\" alt=\"Mayuresh and Miriam along with several former lab members (Shravan, Alex, and Xiaopeng) published an article in ACS Chemical Biology exploring a widespread group of multinuclear nonheme iron-dependent oxidative (MNIO) enzymes that modify peptide substrates.\" title=\"Mayuresh and Miriam along with several former lab members (Shravan, Alex, and Xiaopeng) published an article in ACS Chemical Biology exploring a widespread group of multinuclear nonheme iron-dependent oxidative (MNIO) enzymes that modify peptide substrates.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6157\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/927-20260116165802-260116SRDgraphicalabstract.jpg\" alt=\"Shravan and collaborators from the Pamer lab have published an article in Cell Host & Microbe outlining the relationships between lanthipeptide-producing gut microbes and their effects on microbiome structure.\" title=\"Shravan and collaborators from the Pamer lab have published an article in Cell Host & Microbe outlining the relationships between lanthipeptide-producing gut microbes and their effects on microbiome structure.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6158\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/927-20260116165830-260116aminoacyltRNAMGG.jpg\" alt=\"Dinh and Mayuresh, along with collaborators from the van der Donk, Suga, and Goto labs have published a paper in the Journal of the American Chemical Society that defines how peptide aminoacyl-tRNA ligases (PEARLs) recognize their aminoacyl-tRNA substrates.\" title=\"Dinh and Mayuresh, along with collaborators from the van der Donk, Suga, and Goto labs have published a paper in the Journal of the American Chemical Society that defines how peptide aminoacyl-tRNA ligases (PEARLs) recognize their aminoacyl-tRNA substrates.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6362\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/927-20260116165845-260116daptidesSRD.jpg\" alt=\"Shravan and collaborators from the Mitchell, Chekan, Zhao, and Sarlah labs have published a paper in ACS Central Science where they explore the biosynthesis and engineerability of daptides.\" title=\"Shravan and collaborators from the Mitchell, Chekan, Zhao, and Sarlah labs have published a paper in ACS Central Science where they explore the biosynthesis and engineerability of daptides.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6160\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/927-20260116165902-260116lassoESMSEB.jpg\" alt=\"Susanna and collaborators from the Shukla group have published a paper in Nature Communications in which they developed LassoESM, a large language model specifically tailored for lasso peptides.\" title=\"Susanna and collaborators from the Shukla group have published a paper in Nature Communications in which they developed LassoESM, a large language model specifically tailored for lasso peptides.\" width=\"100%\" \/><\/a><a id=\"vumediaitem_6161\" href=\"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/lab-highlights\/\"><img decoding=\"async\" src=\"https:\/\/cdn.vanderbilt.edu\/vu-web\/clients\/mediadisplays\/927-20260116170102-260116Chl.jpg\" alt=\"Andrew and Mayuresh, with collaborators from the Mchaourab group, have published a paper in Angewandte Chemie International Edition where they characterized the tryptophan halogenase involved in chlorolassin biosynthesis, ChlH, uncovering remarkably broad substrate promiscuity.\" title=\"Andrew and Mayuresh, with collaborators from the Mchaourab group, have published a paper in Angewandte Chemie International Edition where they characterized the tryptophan halogenase involved in chlorolassin biosynthesis, ChlH, uncovering remarkably broad substrate promiscuity.\" width=\"100%\" \/><\/a>\n\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>From Genes to Molecules We are a chemical biology group that focuses on the study of natural products. Natural products are highly evolved and functionally privileged compounds that often display complex chemical structures. These molecules have inspired generations of synthetic organic chemists, unveiled numerous fundamental biological processes as chemical probes, and served as the most&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"open","template":"","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"tags":[],"class_list":["post-2","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/pages\/2","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/comments?post=2"}],"version-history":[{"count":31,"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/pages\/2\/revisions"}],"predecessor-version":[{"id":910,"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/pages\/2\/revisions\/910"}],"wp:attachment":[{"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/media?parent=2"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lab.vanderbilt.edu\/mitchell-lab\/wp-json\/wp\/v2\/tags?post=2"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}