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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 pABA binding site in RFA-P synthase has a relatively large hydrophobic pocket near the amino group. These enzyme-targeted inhibitors arrest the methanogenesis and growth of pure cultures of methanogens. Supplying pABA to the culture relieves the inhibition, indicating a competitive interaction between pABA and the inhibitor at the cellular target, which is most likely RFAP synthase. The inhibitors do not adversely affect the growth of pure cultures of the bacteria (acetogens) that play a beneficial role in the rumen. Inhibitors added to dense ruminal fluid cultures (artificial rumena) halt methanogenesis; however, they do not inhibit volatile fatty acid (VFA) production and, in some cases, VFA levels are slightly elevated in the methanogenesis-inhibited cultures. We suggest that inhibiting methanopterin biosynthesis could be considered in strategies to decrease anthropogenic methane emissions, which could have an environmental benefit since methane is a potent greenhouse gas.

Original languageEnglish (US)
Pages (from-to)7236-7241
Number of pages6
JournalApplied and environmental microbiology
Volume69
Issue number12
DOIs
StatePublished - Dec 1 2003

Fingerprint

p-aminobenzoic acid
4-Aminobenzoic Acid
Methane
methanogenesis
methane production
targeting
inhibitor
biosynthesis
methane
methanogens
Volatile Fatty Acids
volatile fatty acids
Growth
acid
aniline
synthesis
Rumen
Enzyme Inhibitors
greenhouse gases
rumen fluids

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

Cite this

Dumitru, R., Palencia, H., Schroeder, S. D., DeMontigny, B. A., Takacs, J. M., Rasche, M. E., ... Ragsdale, S. W. (2003). Targeting Methanopterin Biosynthesis to Inhibit Methanogenesis. Applied and environmental microbiology, 69(12), 7236-7241. https://doi.org/10.1128/AEM.69.12.7236-7241.2003

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

In: Applied and environmental microbiology, Vol. 69, No. 12, 01.12.2003, p. 7236-7241.

Research output: Contribution to journalArticle

Dumitru, R, Palencia, H, Schroeder, SD, DeMontigny, BA, Takacs, JM, Rasche, ME, Miner, JL & Ragsdale, SW 2003, 'Targeting Methanopterin Biosynthesis to Inhibit Methanogenesis', Applied and environmental microbiology, vol. 69, no. 12, pp. 7236-7241. https://doi.org/10.1128/AEM.69.12.7236-7241.2003
Dumitru, Razvan ; Palencia, Hector ; Schroeder, Scott D. ; DeMontigny, Bree A. ; Takacs, James M ; Rasche, Madeline E. ; Miner, Jess L. ; Ragsdale, Stephen W. / Targeting Methanopterin Biosynthesis to Inhibit Methanogenesis. In: Applied and environmental microbiology. 2003 ; Vol. 69, No. 12. pp. 7236-7241.
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