My research explores how biosynthetic pathways have evolved during the evolution of modern organismal lineages. We study pathways from Methanocaldococcus jannaschii, a hyperthermophilic microorganism that grows at 85°C near hydrothermal vents, using hydrogen to reduce CO₂ to methane. Methanogenic archaea like M. jannaschii produce more than 400 million tons of methane each year. We also study chlamydial metabolism, using genome sequences from these pathogens to identify new pathways and decipher the cells’ physiological relationship with their hosts. Through this work, we have found that convergent and parallel evolution occurred frequently in microbial history. These non-traditional modes of evolution help us understand the significance and modularity of biochemical pathways.

Methanogenic Coenzyme Biosyntheses

Methanogenesis from CO₂ requires six unusual coenzymes and my work explores the biosyntheses of two: Coenzyme M (2-mercaptoethanesulfonic acid) and Coenzyme B (7-mercaptoheptanoylthreonine phosphate). We have recently characterized genes in the 2-oxoacid elongation pathway that includes homocitrate synthase, homoaconitase and homoisocitrate dehydrogenase. This remarkable pathway extends 2-oxoacids by up to three methylene groups to produce the acyl precursor for CoB.

Archaeal Polyamine Biosyntheses

Polyamines are organic cations that stabilize anionic nucleic acids and proteins in all organisms. Many of the enzymes that archaea use to produce polyamines differ significantly from their bacterial and eucaryal counterparts. For example, the euryarchaea use a pyruvoyl-dependent enzyme rather than a pyridoxal-5´-phosphate dependent enzyme to decarboxylate L-arginine in the first step of putrescine biosynthesis. We currently study the enzymology of polyamine biosynthetic reactions, in both euryarchaea and crenarchaea.

Chlamydial Metabolism

Chlamydia are obligate intracellular pathogens that replicate inside an inclusion vacuole in their host cells. Different chlamydial strains infect a variety of mammalian epithelial cells, often causing persistent diseases. We study a unique arginine utilization system found in most chlamydia that involves L-arginine uptake, its decarboxylation, and the export of agmatine. Using biochemical and cell culture techniques we are beginning to explore the physiological roles of this system in resisting acidification or modulating nitric oxide production.