Cofactor Biosynthesis in Methane-Producing Microorganisms
The Rasche laboratory focuses on investigating the biochemistry of methane-producing microorganisms (methanogens). These microorganisms are abundant in landfills, wastewater treatment facilities, and the digestive systems of cattle, and they play beneficial roles by contributing to waste degradation and methane production as a bioenergy source. However, methane is also a potent greenhouse gas, and intestinal methanogens have been correlated with obesity in humans.
The overall research goal is to use biochemical, biophysical, and computational modeling approaches to discover and characterize enzymes needed for the biosynthesis of the coenzyme tetrahydromethanopterin (H4MPT). This molecule is structurally similar to tetrahydrofolate, and it carries one-carbon units through various chemical transformations during methane production. Biochemical understanding of H4MPT biosynthesis has produced methanogen inhibitors intended to reduce greenhouse gas emissions, and future research may guide the discovery of drugs for treatment of obesity-associated diseases.
Selected publications (Click for full list)
Wang, S., Tiongson, J., and Rasche M.E. Discovery and characterization of the first archaeal dihydromethanopterin reductase (DmrX), an iron-sulfur flavoprotein from Methanosarcina mazei. J. Bacteriol. 2014 196 204-209
McNamara, D.E., Cascio, D., Jorda, J., Bustos, C., Wang, T., Rasche, M.E., Yeates, T.O, and Bobik, T.A. 2014. Structure of dihydromethanopterin reductase: a cubic protein cage for redox transfer. J. Biol. Chem. 2014 289, 8852-8864
Bobik, T.A., Morales, E., Shin, A., Cascio, D., Sawaya, M. R., Arbing, M., Yeates, T.O. and Rasche, M. E. Structure of the methanofuran/methanopterin biosynthetic enzyme MJ1099 from Methanocaldococcus jannaschii. Acta Crystallographica F 2014 F70, 1472-1479
Chistoserdova, L., Rasche, M.E., and Lidstrom, M.E. Novel tetrahydromethanopterin biosynthesis genes discovered via mutagenesis in Methylobacterium extorquens AM1. J. Bacteriol. 2005 187, 2508-2512
Dumitru, R., Palencia., H., Schroeder, S. D., DeMontigny, B., Takacs, J., Rasche, M. E., Miner, J. L., and Ragsdale, S. W. Targeting methanopterin biosynthesis to inhibit methanogenesis. Appl. Environ. Microbiol. 2003 69, 7236-7241