People » Jonathan Caranto


  • Roles of nitric oxide in microbial physiology
  • Metalloenzymology – intermediate trapping and mechanism
  • Natural product biosynthesis
  • Physiological roles of bacterial natural products

Our current arsenal of antibiotics may soon be obsolete with the rise of antibiotic-resistant bacteria, thereby requiring the discovery and development of new antibiotics. To provide new antibiotics and other drug candidates, our lab, led by Dr. Caranto, studies the biosynthesis of bacterial natural products (NPs). We use interdisciplinary approaches to 1) discover new NPs and their biosynthetic pathways, 2) detect new enzymatic activities, and 3) elucidate enzyme mechanisms using millisecond-mixing techniques and spectroscopies from the bioinorganic toolkit. The estimated number of NPs that remain to be discovered is astronomical. To focus our research, we study enzymes that catalyze nitrations, N–N bond formations, or require nitric oxide for their activities.

  1. Vilbert, A.C.; Caranto, J.D.; Lancaster, K.M. The Lysine Cross-Link to Heme P460 Obviates NO-Dependent Histidine-Dissociation from Nitrosomonas europaea Cytochrome P460 {FeNO}7. Sci. 2018, Advance Article. http://pubs.rsc.org/en/content/articlelanding/2018/sc/c7sc03450d
  2. Weitz, A.C; Giri, N.; Caranto, J.D.; Kurtz, D.M., Jr.; Bominaar, E.L.; Hendrich, M.P. Spectroscopy and DFT calculations of a flavo-diiron enzyme implicate new diiron site structures, Am. Chem. Soc. 2017, 139, 12009–12019. http://pubs.acs.org/doi/abs/10.1021/jacs.7b06546
  3. Caranto, J.D.; Lancaster, K.M. Nitric oxide is an obligate bacterial nitrification intermediate produced by hydroxylamine oxidoreductase, Natl. Acad. Sci. U.S.A. 2017, 114, 8217–8222. http://www.pnas.org/content/114/31/8217
  4. Caranto, J.D; Vilbert, A.C.; Lancaster, K.M. Nitrosomonas europaea cytochrome P460 is a direct link between nitrification and nitrous oxide emission, Natl. Acad. Sci. U.S.A. 2016, 113, 14704–14709. http://www.pnas.org/content/113/51/14704
  5. Caranto, J.D.; Weitz, A.; Giri, N.; Hendrich, M.P.; Kurtz, D.M., Jr. A diferrous-dinitrosyl intermediate in the N2O-generating pathway of a deflavinated flavo-diiron protein, Biochemistry 2014, 53, 5631–5637. http://pubs.acs.org/doi/10.1021/bi500836z
  6. Caranto, J.D.; Weitz, A.; Hendrich, M.P.; Kurtz, D.M., Jr. The nitric oxide reductase mechanism of flavo-diiron protein: Identification of active-site intermediates and products, Am. Chem. Soc. 2014, 136, 7981–7992. http://pubs.acs.org/doi/abs/10.1021/ja5022443
  7. Fang, H.; Caranto, J.D.; Mendoza, R.; Taylor A.B.; Hart, P.J.; Kurtz, D.M., Jr. Histidine ligand variants of a flavo-diiron protein: effects on structure and activities, Biol. Inorg. Chem. 2012, 17, 1231-1239. http://www.springerlink.com/content/4m588426u1345054/fulltext.pdf
  8. Caranto, J.D.; Gebhardt, L.L.; MacGowan, C.E.; Limberger, R.J.; Kurtz, D.M., Jr. Treponema denticola superoxide reductase: In vivo role, in vitro reactivities and a novel [Fe(Cys)4] site, Biochemistry, 2012, 51, 5601-5610. http://pubs.acs.org/doi/pdf/10.1021/bi300667s
  9. Hayashi, T.; Caranto, J.D.; Matsumara, H.; Kurtz, D.M. Jr.; Moenne-Loccoz, P. Vibrational analysis of mononitrosyl complexes in hemerythrin and flavodiiron proteins: relevance to detoxifying NO reductase, Am. Chem. Soc. 2012, 134, 6878-6884. http://pubs.acs.org/doi/pdf/10.1021/ja301812p
  10. Hayashi, T.; Caranto, J.D.; Wampler, D.A.; Kurtz, D.M. Jr.; Moenne-Loccoz, P. Insights into the nitric oxide reductase mechanism of flavo-diiron proteins from flavin-free enzyme, Biochemistry 2010, 49, 7040-7049. http://pubs.acs.org/doi/pdf/10.1021/bi100788y

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