Hydrocarbon Biosynthesis
The enzymatic production of hydrocarbons (alkanes and alkenes) from fatty acid metabolites provides one strategy for the efficient production of fungible "drop-in" fuels. One enzyme under investigation in the lab (termed OleT) metabolizes fatty acids to alkenes and carbon dioxide, a reaction which is highly atypical for the enzyme class. We are studying the detailed molecular mechanism of OleT and related enzymes, optimizing its activity, and assembling a pathway for the efficient production of fuels in vivo.
Functional Evolution of Diiron Enzymes
The carboxylate-bridged dinuclear iron cluster is one of the most functionally versatile cofactors found in biology. We are examining the origins for reaction diversification in diiron enzymes using a set of proteins with very similar overall protein architectures (an α4 helical motif) and active site structures. Despite this similarity, the enzymes under study catalyze very different types of chemistry, orchestrating the biosynthesis of signaling molecules, hydrocarbons, antibiotics, and virulence factors in pathogenic bacteria.
Antibiotic Tailoring
Many pharmaceuticals deployed in the clinic derive from natural products that are assembled in an iterative fashion by non-ribosomal peptide synthetases (NRPS) and accessory tailoring enzymes. We are interested in understanding the remarkable diversity of non-ribosomal peptide tailoring reactions and the molecular basis for enzyme:NRPS interactions in efforts to develop combinatorial libraries of new natural products.
Biophysical Spectroscopy
Our interests in transient kinetics and biophysical methods (e.g. EPR) has given us the opportunity to investigate a number of interesting systems, including transition metal-containing enzymes, organic frameworks, and rare earth metals.
Fats to Fuel
As part of an NSF CAREER grant on the mechanism of alkene synthesis from fatty acids catalyzed by OleT, we are seeking public participation in an ongoing protein design experiment. We have characterized several catalysts that are able to generate hydrocarbons, albeit with highly variable efficiencies. Using one of these enzymes (CYP-MP) as a scaffold, which is also the poorest alkene producer that we know of, we are asking the public to design mutants of CYP-MP which we will generate, test, and publish the results online.