Control of rumen methanogenesis by inhibiting the growth and activity of methanogens with hydroxymethylglutaryl-SCoA inhibitors

The CH4-forming bacteria in the rumen are Archaea. All Archaea have unique membrane lipids that contain glycerol joined by ether linkages to long chain isoprenoid alcohols. Mevalonate is a key precursor for isoprenoid synthesis by methanogens and is also essential for the production of cholesterol by humans. Mevalonate is produced by reduction of hydroxymethylglutaryl-SCoA (HMG-CoA). HMG-CoA reductase is a target of HMG-CoA inhibitors (statins) used to inhibit human cholesterol synthesis. Statins would be expected to specifically inhibit growth of rumen methanogenic bacteria by inhibiting their synthesis of mevalonate. Rumen fermentative bacteria would not be inhibited because they are eubacteria and most of their lipids are glycerol esters of long chain fatty acids. These predictions are supported by the results of our study of the effect of statins on the growth of pure cultures of rumen methanogenic and fermentative bacteria. The HMG-CoA reductase inhibitors, mevastatin and lovastatin (ca. 10 nM), inhibited the growth of strains of rumen Methanobrevibacter. They did not inhibit the growth of strains of Ruminococcus albus, R. flavefaciens, Butyrivibrio fibrisolvens, Fibrobacter succinogenes and Selenomonas ruminantium. These eubacterial species are essential for ruminal fermentation of cellulose, starch and other plant polysaccharides.