Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms and play an essential role in DNA replication and DNA repair. They are able to harness the amazing reactivity of free radicals to effect chemically difficult reactions with exquisite specificity. They utilize diverse metallo-cofactors to generate an essential protein-based thiyl radical that initiates substrate reduction. In class I RNRs, a diferric-tyrosyl radical cofactor is proposed to generate the thiyl radical by means of a 35 Å proton-coupled electron transfer pathway, which is unprecedented in biology. Because of their central role, they are also successful targets of several drugs used clinically in the treatment of a number of malignancies.

Current projects in the group include:
Postulated Proton-Coupled Electron Transfer Pathway in Class I RNR

Proposed biosynthesis, activation, and regulation of RNR in E. coli

Polyhydroxyalkanoates (PHAs), including polyhydroxybutyrates (PHBs) and polyhydroxyvalerates (PHVs), are biodegradable polymers with thermoplastic and/or elastomeric properties. They are synthesized by various bacteria under nutrient-limited conditions as a carbon storage material and are deposited as amorphous granules within the bacteria. Currently, companies such as Metabolix and Proctor and Gamble are pursuing the commercialization of PHAs as competitive plastics. Our research aim is to understand the mechanisms of PHA homeostasis. These mechanisms provide an important paradigm for non-template driven polymerization processes in biology. Ultimately, we would like to apply our knowledge about PHA homeostasis to engineer new biodegradable polymers and produce them in an economically competitive fashion.

Tools we use in the PHB project: