Inhibition of Methanogenesis in Ruminant Animals

描述(申请人提供)：该项目的目标是开发一种在反刍动物中形成甲烷的新型抑制剂。目前，莫能菌素是一种相对非特异性的抗生素，在畜牧业中被广泛使用。莫能菌素通过减少甲烷和增加丙酸产量来提高农业生产率；然而，它也抑制乙酰化，这对动物来说是一个有益的过程。我们将针对一种特定的生物合成酶，它催化产甲烷微生物生存的关键步骤，产甲烷微生物是古生物界的成员，但不存在于真核生物或细菌中。一种特定的甲烷生成抑制剂将具有莫能菌素的好处，可以提高生产率，而不会受到抗生素使用的不利影响。它应该有很大的市场价值。目前预计的用途将是饲养场的牛、猪和羊。这种抑制剂也可以用来减少人类胃肠道中的甲烷产量。由于家畜是全球最大的甲烷来源，抑制反刍动物的甲烷生成有可能减轻温室效应。我们的计划是合成和表征这种生物合成酶的抑制剂，这种酶可以在浓度低于100纳摩尔的情况下阻止甲烷生成。

DESCRIPTION (provided by applicant): The goal of this project is to develop a novel inhibitor of methane formation in ruminant animals. Currently, monensin, a relatively nonspecific antibiotic, is widely used in the livestock industry. Monensin increases agricultural productivity by decreasing methane and increasing propionate production; however, it also inhibits acetogenesis, which is a beneficial process for the animal. We will target a specific biosynthetic enzyme that catalyzes an essential step for survival of methanogenic microbes, which are members of the kingdom Archaea, yet is not present in eukaryotes or bacteria. A specific methanogenesis inhibitor would have the benefits of monensin on increased productivity without the detrimental effect of antibiotic use. It should have significant market value. The immediate projected use would be on feedlot cattle, pigs, and sheep. Such an inhibitor could also be used to decrease methane production in the human GI tract. Since domesticated livestock is the largest global source of methane, inhibiting methanogenesis by ruminant animals has the potential of mitigating the greenhouse effect. Our plan is to synthesize and characterize inhibitors of the biosynthetic enzyme that arrest methanogenesis at a concentration below 100 nanomolar.