Menaquinone Physiochemical Properties Alter Energy Metabolism in Actinobacteria

化学系的生命过程化学项目为该奖项提供资金。科罗拉多州立大学的黛比·克兰斯教授和迪恩·克里克教授研究了特定分子如何在微生物的营养物质(代谢能量)产生能量的过程中发挥关键作用。产生新陈代谢能量的第一步是电子传递--电子通过一系列嵌入在膜中的小分子和蛋白质逐步传递。这些分子中的一个是孟喹酮。很长一段时间以来，人们就知道菜籽酮参与了电子传递步骤，但它是如何参与这一过程的仍不清楚。本研究对菜籽酮分子的结构和反应活性进行了研究。临界电子转移反应对孟喹酮的结构非常敏感。这种敏感性的基础是通过对分子形状进行微小变化并测量对代谢能量产生的影响来检验的。这些研究允许本科生、研究生和博士后研究员在合成、溶液中和人造膜界面的分子结构分析以及微生物学方法学方面获得专门培训。该主题在适当的环境中向公众介绍，包括与K-12学生和其他社区群体的外展计划。结核分枝杆菌的Menj(Rv0561c)酶催化含有9个异戊二烯单元(MK-9)的Menuone还原转化为具有9个异戊二烯单元的Menuone，其中第二个异戊二烯单元饱和(MK-9(II-H2))。MK-9(II-H2)结构的细微变化导致生物体的生存和能量代谢发生惊人的戏剧性变化。单键到双键的转换(MK-9(II-H2)到MK-9)如何对分枝杆菌的能量代谢产生如此深远的影响尚不清楚。目前的研究项目试图确定区域特异性饱和在MK衍生物中的生物学作用。研究了简单合成的MK衍生物的物理性质，目的是阐明饱和对溶液结构、氧化还原电位和水/脂界面分子相互作用的影响。这些研究的结果被用来发展对这些变化如何影响MK的生物学活动的理解。目前的假设是，分子的形状指导着生物反应。

The Chemistry of Life Processes Program in the Chemistry Division funds this award. Professors Debbie Crans and Dean Crick from Colorado State University investigate how a specific molecule plays a crucial part in the generation of energy from nutrients (metabolic energy) in microorganisms. The first step in production of metabolic energy is electron transport- where electrons are passed stepwise through a series of small molecules and proteins embedded in a membrane. One of these molecules is menaquinone. It has been known for a long time that menaquinone is involved in the electron transport steps, but how it participates in the process is still unknown. The structure and reactivity of the menaquinone molecule is investigated in this research. The critical electron transfer reaction is exquisitely sensitive to the structure of menaquinone. The basis for this sensitivity is examined by making small variations in the shape of the molecule and measuring the effects on the metabolic energy generation. These studies allow undergraduate students, graduate students and postdoctoral fellows to acquire specialized training in synthesis, analysis of molecular structures in solution and at the interfaces of artificial membranes, and microbiological methodology. The topic is presented to the public in suitable settings including outreach programs with K-12 students and other community groups.The enzyme MenJ (Rv0561c) of Mycobacterium tuberculosis catalyzes the reductive conversion of menaquinone with nine isoprene units (MK-9) to menaquinone with nine isoprene units with the second isoprene unit saturated (MK-9(II-H2)). A subtle variation in the structure of MK-9(II-H2) results in surprisingly dramatic changes in survival and energy metabolism for the organism. How the conversion of a single bond to a double bond (MK-9(II-H2) to MK-9) could have such profound effects on the energy metabolism of mycobacteria is not understood. The current research project seeks to define the biological role of regiospecific saturation in MK derivatives. The physical properties of simple synthetic MK derivatives are investigated with the objective of elucidating the effects of saturation on solution structure, redox potentials, and molecular interactions at water/lipid interfaces. The results from these studies are used to develop an understanding for how these changes can affect MK's biological activities. The current hypothesis is that the shape of the molecule directs the biological responses.