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
Chorismate mutase-prephenate dehydratase from Escherichia coli. Study of catalytic and regulatory domains using genetically engineered proteins.
Authors: Authors: Zhang S, Pohnert G, Kongsaeree P, Wilson DB, Clardy J, Ganem B.
J Biol Chem
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Chemical inducers of dimerization: the atomic structure of FKBP12-FK1012A-FKBP12.
Authors: Authors: Schultz LW, Clardy J.
Bioorg Med Chem Lett
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Using scalarane sesterterpenes to examine a sponge taxonomic anomaly.
Authors: Authors: Jaspars M, Jackson E, Lobkovsky E, Clardy J, Diaz MC, Crews P.
J Nat Prod
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Antifungal diterpenoid alkaloids from Delphinium denudatum.
Authors: Authors: Nasreen A, Akhtar F, Shekhani MS, Clardy J, Parvez M, Choudhary MI.
J Nat Prod
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Pyrrolosporin A, a new antitumor antibiotic from Micromonospora sp. C39217-R109-7. II. Isolation, physico-chemical properties, spectroscopic study and X-ray analysis.
Authors: Authors: Schroeder DR, Colson KL, Klohr SE, Lee MS, Matson JA, Brinen LS, Clardy J.
J Antibiot (Tokyo)
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Production of kanosamine by Bacillus cereus UW85.
Authors: Authors: Milner JL, Silo-Suh L, Lee JC, He H, Clardy J, Handelsman J.
Appl Environ Microbiol
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Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP.
Authors: Authors: Choi J, Chen J, Schreiber SL, Clardy J.
Science
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A cholesteryl ester transfer protein inhibitor from an insect-associated fungus.
Authors: Authors: Lee JC, Coval SJ, Clardy J.
J Antibiot (Tokyo)
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Site-directed mutagenesis of monofunctional chorismate mutase engineered from the E. coli P-protein.
Authors: Authors: Zhang S, Kongsaeree P, Clardy J, Wilson DB, Ganem B.
Bioorg Med Chem
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Comparison of the structures of the cyclotheonamide A complexes of human alpha-thrombin and bovine beta-trypsin.
Authors: Authors: Ganesh V, Lee AY, Clardy J, Tulinsky A.
Protein Sci
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