The Berkowitz group explores problems at the Chemistry/Biology interface. We are particularly engaged at the nexus of synthetic organic chemistry and mechanistic enzymology. The group has a longstanding interest in the synthesis and evaluation of small molecule tools for Chemical Biology. These include probe molecules bearing unnatural functionality designed to either mimic critical native functional groups (e.g. fluorinated phosphonates as phosphatase-inert surrogates for biological phosphates) or to inactivate specific target enzymes (e.g. alpha-vinylic amino acids as mechanism-based inactivators for PLP-dependent enzymes). More recently, the group has become actively engaged in the enlistment of enzymes in the service of asymmetric organic synthesis, both as chiral catalysts for unnatural and often complex organic substrates, and as chiral “sensors” to facilitate the catalyst discovery and reaction development enterprise (i.e. ISES = In Situ Enzymatic Screening). Students and postdoctoral fellows in the group gain training and exposure to modern asymmetric synthesis, protein biochemistry, enzyme kinetics and molecular biology.