December, 2017. See the Nature Chemical Biology Research Highlight of our work on the molecular mechanisms of colibactin resistance.
November, 2017. See the Yale news article about our collaborative research on the elucidation of luciferin biosynthesis.
November, 2017. Congrats Prabhanshu, Emilee, Alan, and Chung Sub on your recent JACS communication, leading to the discovery of a novel enzyme – a cyclopropane hydrolase – that confers resistance to colibactin. Structure-function studies are described for the new enzyme and its biochemical reaction. Colibactin has been linked to colorectal cancer pathogenesis, and the mechanistic insights gained from these studies not only support a resistance mechanism at the molecular level, but also significantly expand our knowledge on colibactin’s mode of action.
November, 2017. Congrats Corey and Hyun Bong on your Biochemistry article, biochemically characterizing the first pteridine-nonribosomal peptide hybrid pathway from the entomopathogen Photorhabdus luminescens. The paper provides important insights for the novel pathway’s biological functions at the protein, metabolic, and cellular levels. Interestingly, the bacterial cellular redox pathway appears to regulate pathways associated with quorum sensing, antibiosis, and nematode host development.
September, 2017. Congrats Eric on your Biochemistry Viewpoint on a novel nucleoside antibiotic that targets bacterial RNA polymerase. Yet again, natural products come to the rescue for identifying novel drug binding sites and modes of action for targeting pathogenic bacteria.
August, 2017. Congrats Sandhya and Alan on your ACS Chem Bio article defining the structure and function of an unusual intermediate-releasing thioesterase (TE) at the molecular level from the colibactin biosynthetic pathway. This paper provides new insights into the post-translational regulatory aspects of a bacterial genotoxic pathway in the gut linked to colorectal cancer formation. The enzyme was shown at the biochemical level to regulate the release of critical intermediates required for genotoxicity while removing aberrant enzyme products that shut down the enzymatic system.
July, 2017. Congrats to Eric Trautman for successfully defending his PhD thesis. Good luck with your next steps in consulting.
July, 2017. We welcome Alexandra (Alex) Gatsios to the lab as a Chemical Biology graduate student from Smith College.
May, 2017. Congrats Jason for receiving a Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease (PATH) Award. Our PATH project focuses on defining cell-to-cell stress communications in pathogenic bacteria and in human-bacteria interactions. Jason would like to thank Jaymin Patel for bringing a 30-thousand foot vision on paper to nearing practical solutions at the bench. Jason would also like to thank Chung Sub Kim, Hyun Bong Park, and Corey Perez on their associated bacterial cell-to-cell stress communication work. See the associated YaleNews article.
May, 2017. Congrats Jason for receiving the Camille Dreyfus Teacher-Scholar Award.
April, 2017. Congrats Jason for being named as a William Raveis Charitable Fund scientist through the Damon Runyon Cancer Research Foundation. The William Raveis Charitable Fund in partnership with the Damon Runyon Foundation has planned a series of events across the Northeast to raise awareness about the importance of more broadly supporting cancer research.
February, 2017. Congrats Hyun Bong, Corey, and Karl on your paper being accepted to eLife. This study identifies the first example of a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster. The paper describes synteny-based genome mining, genetics, pathway-targeted metabolomics, and quantitative proteomics analyses that led to the new metabolite structures encoded by the unprecedented pathway, the “pepteridines,” in Photorhabdus luminescens. The pepteridines are produced only in a phenotypic variant associated with bacterial pathogenesis and not in the variant associated with mutualistic colonization. Genetics and proteomics further supported that the pathway was under the control of a LysR-type regulator associated with the mutualist-pathogen transition and affected the regulation of proteins that govern pyrone quorum sensing and other defensive genetic loci. See also Yale West Campus News.
February, 2017. Congrats Hyun Bong, Parthasarathy, Corey, Joon Ha, and Jeannie on your paper being accepted to J. Biol. Chem. This was a multi-group collaboration with Steven Almo, Elissa Hallem, and Jeffrey Bonanno. The paper describes the X-ray structure and biochemical characterization of an orphan FAD-dependent monooxygenase that catalyzes the stereoselective epoxidation of stilbenes in Photorhabdus luminescens. Stilbenes participate in antibiosis, immunomodulation, and nematode developmental biology in this system. The newly described (bio)chemistry was examined in two distinct animal models. The data support a stilbene detoxification route in the bacteria-nematode symbiosis.
February, 2017. Congrats Eric, Alan, and Emilee on your domain-targeted metabolomics paper being accepted to JACS. This paper combines multiplex automated genome engineering with pathway-targeted analyses to delineate the heterocycle assembly steps of colibactin biosynthesis. In addition to illuminating unexpected catalytic timing events in colibactin biosynthesis, the study also unveiled and structurally confirmed new reactive precolibactins. Upon peptidase treatment, these reactive metabolites were converted to a genotoxic scaffold consistent with the pathway’s genotoxic role associated with colorectal cancer. The domain-targeted metabolomics approach is general and could be widely applied to “multidomain” pathways for unprecedented genetic and metabolic precision analyses. See also the JACS Spotlight.
January, 2017. Congrats Thomas, Stephanie, and Christina on your paper being accepted to ChemBioChem. This paper describes an “orphan” gene cluster in Legionella pneumophila, the causative agent of Legionnaires’ disease. The single gene cluster produces two distinct groups of aromatic amino acid-derived metabolites, including new N-acyl-amide and known isocyanide metabolites. One of the new N-acyl-amides harbored a cyclopropane moiety derived from cyclopropane fatty acid synthase. The paper also develops a general tetrazine-based chemoselective ligation approach to identify isocyanide-functionalized metabolites.
December, 2016. Congrats Caleb on your paper being accepted to eLife. This paper shows how intermicrobial chemical exchange in the microbiome can regulate animal behaviors. Such interactions are missed in the more common single microbe metabolic studies.
November, 2016. Congrats Alan, Herman, and Jaymin on your colibactin paper being accepted to JACS. This paper provides a robust mechanistic model for colibactin genotoxic reactivities and unifies the currently observed small molecule chemistry of the colibactin pathway.
June, 2016. Congrats Hyun Bong, Corey, and Elena on your amicoumacin paper being accepted to Molecules. This paper illuminates a new amicoumacin antibiotic resistance mechanism and also provides the first mode of action insights for N-acyl-D-Asn pro-drug motifs in nonribosomal peptide-polyketide hybrid metabolites.
June, 2016. Congrats Hyun Bong on your pyrazinone paper being accepted to J. Antibiot. This paper demonstrates that novel pyrazinones in Photorhabdus pathogens are only produced in a phenotypic variant associated with pathogenesis and provides new insights for how this class of protease inhibitors may participate in host-bacteria interactions.
May, 2016. We welcome Tyler Goddard to the lab as a Chemical Biology graduate student from Baylor University.
May, 2016. We welcome Phu Khat Nwe to the lab as a Chemical Biology graduate student from Albion College.
May, 2016. We welcome Jhe-Hao Li to the lab as a Chemical Biology graduate student from the National Taiwan University.
April, 2016. We welcome Chung Sub Kim to the lab as a postdoctoral associate from the Kang Ro Lee lab at the Sungkyunkwan University.
March, 2016. Congratulations Emilee Shine on receiving a NSF Graduate Research Fellowship.
March, 2016. Congratulations Alan and Maria on your precolibactin synthesis paper being published in JACS. This paper demonstrates that the colibactin warhead undergoes a cyclization cascade, assembling from acyclic precursors, and that the colibactin peptidase can process advanced precolibactin C into N-myristoyl-D-Asn and colibactin C.
February, 2016. We welcome Christina Cho to the lab as a Chemistry graduate student from Macaulay Honors College at Queens College. We also welcome Helen Zhao as an undergraduate researcher in the lab.
January, 2016. Congratulations Jason for receiving a Damon Runyon-Rachleff Innovation Award. Go “M-PAIR” cancer team!
October, 2015. We welcome Joonseok Oh to the lab as a postdoctoral associate from the Hamann lab at the University of Mississippi.