Physical Sciences and Mathematics Commons^™

Targeting Methanopterin Biosynthesis To Inhibit Methanogenesis, Razvan Dumitru, Hector Palencia, Scott D. Schroeder, Bree A. Demontigny, James M. Takacs, Madeline E. Rasche, Jess L. Miner, Stephen W. Ragsdale

James Takacs Publications

This paper describes the design, synthesis, and successful employment of inhibitors of 4-( β -D-ribofuranosyl) aminobenzene-5’-phosphate (RFA-P) synthase, which catalyzes the first committed step in the biosynthesis of methanopterin, to specifically halt the growth of methane-producing microbes. RFA-P synthase catalyzes the first step in the synthesis of tetrahydromethanopterin, a key cofactor required for methane formation and for one-carbon transformations in methanogens. A number of inhibitors, which are N-substituted derivatives of p-aminobenzoic acid (pABA), have been synthesized and their inhibition constants with RFA-P synthase have been determined. Based on comparisons of the inhibition constants among various inhibitors, we propose that the …