New routes to driving enzyme-catalysed chemical synthesis using hydrogen gas

细菌细胞扮演着微型化工厂的角色，并进化出专门的路线来制造我们用于制药、芳香、食品添加剂或用于农业的化学品等多种分子。进行这项工作的细胞的关键部分是酶。打破细胞并分离出一种酶来制造特定的分子是可能的。细菌也可以被改造成制造人造化学品，扩大它们可以生产的分子的范围。现在，大规模培养细菌和分离大量酶的程序已经成熟，与此同时，化学公司开始意识到使用酶而不是传统化学路线的好处。在药物、香水和食品调味品等复杂分子的生产中，酶产生的废物要少得多，产生更纯粹的化学产品，并允许化学作用在水中进行，而不是有毒、污染的溶剂。在食品和制药行业，最终产品的纯度尤其重要，因为这些行业的污染物可能会产生严重的有害影响。尽管人们对在化工生产中使用酶催化越来越感兴趣，但在这种方法被广泛采用之前，仍有许多挑战需要克服。一旦从它们的细胞中分离出来，酶往往非常不稳定。它们的稳定性可以通过将它们附着到表面来提高，但这通常需要复杂的附着过程，而且可能会很昂贵。其次，许多酶只能在被称为辅因子的特殊辅助分子存在的情况下工作，辅因子在制造化学物质的过程中被酶消耗。辅因子也很昂贵，为了使酶过程在经济上可行，必须有某种方法回收辅因子。不幸的是，目前可用的回收辅因子的方法造成了更多的浪费，污染了所需的化学产品。我们已经开发了一种技术来应对这两个挑战，为酶催化提供了亟需的步骤改变。目前，我们的技术只在我们的实验室进行了小规模的演示，但我们现在需要让化学、制药和食品行业相信，这对化学生产的未来提供了真正的好处。我们的技术是这样运作的：一旦我们从细菌细胞中分离出酶，我们立即将它们连接到廉价的碳珠上。这是一个非常简单的一步过程。我们将几种不同类型的酶连接到每个珠子上，以便这些酶可以一起工作来执行制造化学品的每一步。我们向珠子提供低水平、安全的氢气，这为回收辅因子和驱动必要的酶机械提供能量，以制造所需的化学品。为了制造所需的化学品，我们首先将廉价的化学积木放入水中，我们在少量氢气中冒泡，加入酶修饰的珠子，几个小时后，所需的化学产品就可以收集了！酶修饰的珠子可以很容易地从反应混合物中挖出来，除了所需的产物和少量无害的辅因子外，什么也没有留下。作为一个额外的好处，珠子可以被收集和重复使用多次，最大限度地减少使用酶的成本。要将我们的概念从实验室规模的想法转变为可供工业采用的技术，我们需要证明我们可以大规模生产酶。我们需要展示珠子产生化学物质的速度有多快，以及产品有多纯。这个项目将回答这类问题，这样在5年结束时，我们可以说服潜在客户(化学、制药和食品添加剂公司)，我们的技术将使他们能够以更低的成本和更环保的方式制造化学品。

Bacterial cells act as miniature chemical factories and have evolved specialised routes to making many of the sorts of molecules that we use as pharmaceuticals, pleasant fragrances, food additives or chemicals for use in agriculture. The key parts of the cells for carrying out this work are the enzymes. It is possible to break cells open and isolate an enzyme for making a specific molecule. Bacteria can also be engineered to make artificial chemicals, expanding the range of molecules they can produce. Procedures are now well-established for growing bacteria on a large scale and isolating large quantities of enzymes, and at the same time, chemical companies are starting to realise the benefits of using enzymes instead of traditional chemical routes. In the production of complicated molecules such as drugs, fragrances and food flavourings, enzymes generate much less waste, make purer chemical products, and allow chemistry to be carried out in water rather than toxic, polluting solvents. The purity of the end product is particularly important in the food and pharmaceutical industries where contaminants may have serious, harmful effects. Although there has been increasing interest in using enzyme catalysis in chemical production, many challenges remain to be overcome before this approach can be widely adopted. Once isolated from their cells, enzymes are often quite unstable. Their stability can be improved by attaching them to surfaces, but this often requires complicated attachment processes and can be expensive. Secondly, many enzymes only work in the presence of special helper-molecules called cofactors which are used up by the enzymes in the process of making chemicals. The cofactors are also expensive, and for enzyme processes to be economically viable, it is essential to have some way of recycling the cofactors. Unfortunately, the currently-available methods for recycling the cofactors make even more waste which contaminates the desired chemical products. We have developed a technology that addresses both of these challenges, offering a much-needed step change for enzyme catalysis. At the moment, our technology has only been demonstrated on a small scale in our laboratories, but we now need to convince the chemical, pharmaceutical and food industries that this offers real benefits for the future of chemical production. Our technology works as follows: once we have isolated enzymes from the bacterial cells, we immediately attach them onto cheap carbon beads. This is a very simple one-step process. We attach several different types of enzyme to each bead so that the enzymes can work together to carry out each step in making chemicals. We supply the beads with low, safe levels of hydrogen gas, and this provides the energy for recycling the cofactors and to drive the enzyme machinery necessary to make the required chemicals. To make a desired chemical, we start by putting a cheap chemical building-block in water, we bubble in a little hydrogen gas, add our enzyme-modified beads, and after a few hours, the desired chemical product is ready to collect! The enzyme-modified beads can be easily scooped out of the reaction mixture, leaving nothing else except the desired product and a tiny trace of the harmless cofactor. As an added bonus, the beads can be collected and re-used a number of times, minimising the cost of using enzymes. To take our concept from a lab-scale idea to a technology ready for industry to adopt, we need to show that we can produce the enzymes on a large scale. We need to show how quickly the beads can produce chemicals, and how pure the products are. This project will answer these sort of questions, so that at the end of the 5 years, we can convince potential customers (chemical, pharmaceutical and food additive companies) that our technology will allow them to make chemicals more cheaply and in a more environmentally-friendly way.