RUI: Electron Transfer and Inhibition of Dihydromethanopterin Reductase

甲烷产生微生物(产甲烷菌)将甲烷作为替代能源和温室气体进行合成。除了对环境的影响外，这些微生物在医学上也很重要，因为人类肠道中的产甲烷菌与肥胖有关。首席研究员实验室的研究重点是发现微生物产生甲烷所需的蛋白质，以及开发化学抑制剂，这些抑制剂可能会减少甲烷对未来温室气体和肥胖的贡献。这项研究是由加州州立大学富勒顿分校的高中生、本科生和研究生进行的，加州州立大学富勒顿分校是一所主要的本科院校，也是一所为拉美裔服务的大学。这项研究有助于减少生物甲烷的产生，并有助于美国下一代科学研究人员的发展。通过这一奖项，化学部的生命过程化学计划资助了加州州立大学富勒顿分校的Madeline Rasche教授进行的研究，以了解和化学抑制二氢甲烷蝶呤还原酶。四氢甲烷蝶呤(H4MPT)是微生物合成甲烷作为能源和温室气体所必需的一种不寻常的叶酸类辅因子。黄素蛋白二氢甲烷蝶呤还原酶(DMR)催化H4MPT生物合成的最后一步，该酶是设计用于减少生物甲烷产生的化学抑制剂的潜在靶点。基于异种伯克霍尔德氏菌二氢甲烷蝶呤还原酶B(DmrB)的X射线晶体结构，提出了电子转移的乒乓机制。这项由NSF资助的研究的目标是测试关于细菌蛋白(DmrB)和来自真正产生甲烷的微生物的二氢甲烷蝶呤还原酶(DmrX)的同系物中电子转移机制的结构假说。这项研究是由加州州立大学富勒顿分校的高中生、本科生和研究生组成的综合网络进行的，该大学主要是一所本科院校，也是一所为拉美裔服务的大学。这项研究有助于开发甲烷作为温室气体的化学缓蚀剂，并有助于美国下一代化学研究人员的教育。

Methane-generating microorganisms (methanogens) synthesize methane as both an alternative energy source and a greenhouse gas. In addition to their environmental impacts, these organisms are medically important because methanogens in the human gut have been correlated with obesity. Research in the principal investigator's laboratory focuses on the discovery of proteins needed for microbial methane generation and the development of chemical inhibitors that may decrease methanogen contributions to greenhouse gases and obesity in the future. The research is conducted by high school students, undergraduates, and graduate students at California State University at Fullerton, a primary undergraduate institution and Hispanic-serving university. This research contributes to the reduction of biological methane production and to the development of the next generation of scientific researchers in the United States.With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding research by Professor Madeline Rasche at California State University-Fullerton to understand and chemically inhibit dihydromethanopterin reductase. Tetrahydromethanopterin (H4MPT) is an unusual folate-like cofactor required for the microbial synthesis of methane as an energy source and greenhouse gas. The flavoprotein dihydromethanopterin reductase (Dmr) catalyzes the final step in the biosynthesis of H4MPT, and this enzyme is a potential target for chemical inhibitors designed to mitigate biological methane production. Based on the X-ray crystal structure of dihydromethanopterin reductase B (DmrB) from Burkholderia xenovorans, a ping-pong mechanism for electron transfer has been proposed. The goal of this NSF-funded research is to test structure-based hypotheses about the mechanism of electron transfer in the bacterial protein (DmrB) and in a homolog of dihydromethanopterin reductase (DmrX) from a true methane-producing microorganism. The research is conducted by an integrated network of high school students, undergraduates, and graduate students at California State University at Fullerton, a primarily undergraduate institution and Hispanic-serving university. This research contributes to the development of chemical inhibitors of methane as a greenhouse gas and to the education of the next generation of chemistry researchers in the United States.