Picture of Jon Clardy

Jon Clardy, Ph.D.

Christopher T. Walsh Professor of Biological Chemistry and Molecular Pharmacology

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes. 

Research:

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes.  Organizing themes include: 1) function-based discovery of microbially-produced small molecules and their roles in microbial symbioses , 2) function-based discovery of biologically active small molecules using high-throughput screening,  3) genome-based discovery of bacterially-produced small molecules. 

1.  We have focused on the small molecule exchanges that underlie multilateral symbioses involving bacteria, partly because they are widespread and poorly understood and partly because they lead to the discovery of new useful molecules in the biological context in which they evolved.  Current projects involve the bacterial symbionts of fungus-growing ants, members of the human gut microbiome linked to disease, and interactions between micro-algae and bacteria.

2.  We also continue to discover small molecules in a more medically relevant context: high-throughput screening for a variety of diseases.  In these projects we have focused on antibacterial, antifungal, and antiparasitic agents along with immunomodulators and anticancer agents. 

3.  It is now quite clear that well studied bacteria – the producers of drugs that are used on the ton scale, for example – are genetically capable of producing many more potentially useful small molecules.  The biosynthetic gene can be seen but the associated molecules have never been characterized.  Ways to access these cryptic metabolites is a current focus of the laboratory.

Address: 

Room C-643

240 Longwood Avenue

Boston, MA 02115

Publications View
Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina.
Authors: Authors: Li JY, Strobel G, Harper J, Lobkovsky E, Clardy J.
Org Lett
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Biological activity of guanacastepene, a novel diterpenoid antibiotic produced by an unidentified fungus CR115.
Authors: Authors: Singh MP, Janso JE, Luckman SW, Brady SF, Clardy J, Greenstein M, Maiese WM.
J Antibiot (Tokyo)
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The total synthesis of pantocin B.
Authors: Authors: Sutton AE, Clardy J.
Org Lett
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Sexual attraction in the silkworm moth: structure of the pheromone-binding-protein-bombykol complex.
Authors: Authors: Sandler BH, Nikonova L, Leal WS, Clardy J.
Chem Biol
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Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents.
Authors: Authors: Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J.
Structure
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Producing selenomethionine-labeled proteins with a baculovirus expression vector system.
Authors: Authors: Bellizzi JJ, Widom J, Kemp CW, Clardy J.
Structure
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ZmaR, a novel and widespread antibiotic resistance determinant that acetylates zwittermicin A.
Authors: Authors: Stohl EA, Brady SF, Clardy J, Handelsman J.
J Bacteriol
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Chiral resolution and stereospecificity of 6-phenyl-4-phenylethynyl- 1,4-dihydropyridines as selective A(3) adenosine receptor antagonists.
Authors: Authors: Jiang J, Li AH, Jang SY, Chang L, Melman N, Moro S, Ji X, Lobkovsky EB, Clardy JC, Jacobson KA.
J Med Chem
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Structure of the PIN/LC8 dimer with a bound peptide.
Authors: Authors: Liang J, Jaffrey SR, Guo W, Snyder SH, Clardy J.
Nat Struct Biol
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Synthesis, biological activity, and absolute stereochemical assignment of NPS 1392: a potent and stereoselective NMDA receptor antagonist.
Authors: Authors: Moe ST, Shimizu SM, Smith DL, Van Wagenen BC, DelMar EG, Balandrin MF, Chien Y, Raszkiewicz JL, Artman LD, Mueller AL, Lobkovsky E, Clardy J.
Bioorg Med Chem Lett
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