Metal-hydrido intermediates in enzymes: atomic level mechanistic insight and technological applications of hydrogenases

可再生氢为我们提供了一个没有化石燃料的未来，这不仅是因为我们可能会在汽车中使用氢，还因为氢是阳光为水提供能量的主要化学物质，并被用来制造其他能源丰富的化学品。氢是最简单的分子，也是最重要的工业化学品之一，全球使用的氢气超过7000万吨。它是一些最重要的化学过程的原材料，特别是在制造氨的过程中，氨是必不可少的肥料。目前，大多数氢是从化石燃料中生产的；然而，氢也是未来燃料和原材料中最环保、最容易再生的，因为阳光和水是地球上丰富的资源。我们熟悉学校实验室的电解实验，在这个实验中，氢和氧一起形成，因为电能被转化为化学能：由火花引发的氢和氧的爆炸性复合，释放出大部分原始电能作为热和光。太阳能也可以储存为氢气；事实上，绿色植物在光合作用中以一种变相的方式做到这一点(考虑到‘氢’是通过与二氧化碳结合产生碳氢化合物和碳水化合物来‘储存’的)。来自太阳的能量可以很容易地将海洋中的水转化为氢和氧，但我们不能以任何可检测的速度实现这一点：将水转化为氢不仅需要吸收辐射能量的系统(颜料、半导体)，还需要加速化学反应的催化剂。这个研究项目是关于由微生物产生的催化剂，在常温下以每秒数千的速度将水转化为氢，反之亦然。这些催化剂是巨大的分子--被称为氢酶的酶--它们对于理解和设计未来氢技术的化学非常重要。正是通过氢酶，微生物在各种不同的环境中茁壮成长，并产生氢(生物氢)，为人类造福。相反，氢酶对一些臭名昭著的病原体的作用很重要。在当前的工业应用中使用氢气需要高温和昂贵的资源。就性能而言，工业上可用的最佳催化剂是以铂为基础的，这是一种有限而昂贵的元素。相比之下，氢酶催化氢气和质子(水)之间的相互转化的速度和效率高于铂，但使用常见的元素铁和镍。为了达到这样的速率，镍和铁在特殊的原子环境中被“装扮”起来，这些环境也被掩埋起来，以保护它们免受水和其他可能破坏或破坏特殊环境的小分子的影响。这项研究的具体目的之一是确定两种氢酶(一种只含有铁，另一种含有铁和镍)的活性部位的特殊结构是如何在超过20亿年的进化过程中被生物完善的，从而导致如此高的活性。氢是如何与活性中心的原子相互作用的，不同原子的准确位置有多重要，不同基团的键强度和迁移率有多重要，其他小分子的哪些特殊性质使它们能够阻止与氢的正常反应？有了这些信息，我们可以(A)确定基于具有高达铂的活性的铁或镍的合成催化剂设计的最终规则，(B)改造氢酶，使它们能够在氧气中生存，最终导致整个生物体可持续的大规模光合氢生产，(C)改造氢酶，使其能够作为分离的酶应用于特殊技术，如燃料电池和连续的‘辅因子再生’，这是基于酶的合成一些昂贵化学品的技术要求。

Renewable hydrogen offers us a future free of fossil fuels, not just because we might use hydrogen in our cars, but because hydrogen is the primary chemical formed upon water energisation by sunlight and is used to make other energy-rich chemicals. Hydrogen, the simplest of molecules is also one of the most important industrial chemicals and more than 70 million tonnes are used worldwide. It is a raw material for some of the most important chemical processes, particularly in making ammonia, the essential fertiliser. At present, most hydrogen is produced from fossil fuels; however, hydrogen is also the greenest and most easily renewable of future fuels and raw materials because sunlight and water are earth-abundant resources. We are familiar with the electrolysis experiment in the school laboratory where hydrogen is formed along with oxygen because electrical energy is converted to chemical energy: explosive recombination of the hydrogen and oxygen, initiated by a spark, releases back much of the original electrical energy as heat and light. Solar energy also, can be stored as hydrogen; indeed, green plants do this in a disguised way in photosynthesis (consider that 'hydrogen' is 'stored' by combining it with carbon dioxide to give hydrocarbons and carbohydrates). Energy from the sun is easily able to convert water from the oceans into hydrogen and oxygen yet we this does not happen at any detectable rate: converting water to hydrogen requires not only systems for absorbing radiative energy (pigments, semiconductors) but also catalysts that will accelerate the chemical reactions. This research project is about the catalysts, produced by microorganisms, that convert water into hydrogen, and vice versa, at rates of many thousands per second at normal temperatures. These catalysts are giant molecules - enzymes known as hydrogenases - and they are of great importance for understanding and designing the chemistry of future hydrogen technologies. It is through hydrogenases that microbes thrive in all kinds of different environments and produce hydrogen (biohydrogen) for human benefit. Conversely, hydrogenases are important for the action of some notorious pathogens. Use of hydrogen in current industrial applications requires high temperatures and expensive resources. In terms of performance, the best catalysts available to industry are based on platinum, a limited, expensive element. In contrast, hydrogenases catalyse the interconversion between hydrogen gas and protons (water) at rates and efficiencies higher than platinum but using the common elements iron and nickel. To achieve these rates, nickel and iron are 'dressed up' in special atomic environments that are also buried to shield them from water and other small molecules that may disrupt or destroy the special environment. One of the specific aims of this research is to establish how the special structures of the active sites of the two kinds of hydrogenase (one contains only iron, the other contains iron and nickel) perfected by biology during over two billion years of evolution, lead to such high activity. How does hydrogen interact with the atoms of the active site, how important is the exact positioning of different atoms, how important are bond strengths and mobilities of different groups, what special properties of other small molecules enable them to block the normal reactions with hydrogen ? With this information we can (a) determine definitive rules for the design of synthetic catalysts, based on iron or nickel having activities as high as platinum, (b) engineer hydrogenases so that they can survive oxygen, leading eventually to sustainable, large scale photosynthetic hydrogen production by whole organisms, (c) engineer hydrogenases so that they can be applied, as isolated enzymes, in special technologies such as fuel cells and in continuous 'cofactor regeneration' a technical requirement for enzyme-based synthesis of some expensive chemicals.