Bio-MAANICC - Biocatalytic Manufacturing of beta-Amino Acids: Nucleophilic addition to an Imine for C-C bond formation

许多用于制造日常生活中使用的商品的化学成分的传统方法都是昂贵的，并且会产生大量的废料，需要特别小心才能安全地丢弃。然而，尽管努力将对环境的影响降到最低，但通常仍有不可避免的负面影响，这些必要步骤和效率较低的过程的负担以价格上涨和/或药品、农药、塑料和燃料等各种产品供应受限的形式转嫁给消费者。必须尽可能开发和实施高效且最重要的可持续的替代制造工艺，以减轻这些传统方法的环境负担，并朝着环保路线发展。近年来，生物催化领域的研究因提供替代生产方法而受到关注和赞扬。生物催化的定义特征是利用微生物产生酶（天然的，功能性的蛋白质催化剂），然后用于进行所需的反应，作为传统化学生产方法的替代品。因为这些酶或生物催化剂来自活的生物体，它们所进行的反应通常是非常特定的，使用它们的过程通常是非常温和和“绿色”的，通常使生产方法减少浪费，对环境的影响也小得多。然而，当这些生物催化剂被用来制造自然界中找不到的有价值的材料时，它们通常对一种反应如此特异性的事实可能会产生问题。为了解决这个问题，科学家们开发了许多方法来修饰酶，以改善这些非自然反应的特性。这种做法被称为酶工程，它使研究人员有机会定制生物催化剂，以适应它将被使用的过程，并在化学和制药公司中广泛应用，作为一种使用天然和可再生催化剂以可持续的、具有成本效益的生产方法生产非天然材料的手段。由于生物催化剂在大规模生产中的成功，工业界一直在寻找安装生物催化过程的方法，以及用于催化已知生物催化剂中无法获得的理想新反应的酶。这些添加可以导致开发新的和更好的产品和创新的方法，以等效的生物催化途径取代目前的化学过程。为了实现这一预期的扩展，本文提出的研究旨在开发一系列工程酶，以催化目前已知生物催化剂无法提供的有合成价值的反应。这些生物催化剂的效用将通过在药品和天然产品中发现的高价值化学品的生产来证明。目标是为制造各种化学构件提供一种高效和环保的途径，这将促进研究，以确定和推进其在医疗应用中的潜力。为了实现这一目标，我们将建立一种新的生物催化策略，通过使用一种新的生物催化剂来制备这些化合物，并应用酶工程方法快速优化其活性。开发具有生物成本效益的清洁生产方法也将成为未来生产含有这些宝贵中间体的药品和材料的巨大有益资源，有助于确保这些产品可以在全球范围内获得并具有环境可持续性。

Many of the conventional methods used for creating the chemical components of goods used in daily life are expensive and result in a large amount of wasted material that requires extra care to be safely discarded. Yet despite pursuing efforts toward a minimal environmental effect, there is typically still an unavoidable negative impact, and the burden of these necessary steps and less efficient processes are passed on to consumers in the form of higher prices and/or restricted availability of a wide range of products from medicines, pesticides, plastics and fuels. Alternative manufacturing processes that are efficient and most importantly sustainable must be developed and implemented wherever possible to reduce the environmental burden of these traditional methods and move toward environmentally friendly routes.One area of research that has been gaining attention and praise in recent years for providing alternative production methods is the field of biocatalysis. The defining characteristic of biocatalysis is the use of microorganisms to produce enzymes (natural, functioning protein catalysts) that are then used to perform desirable reactions as a replacement for conventional chemical production methods. Because these enzymes, or biocatalysts, come from living organisms, the reactions they perform are generally very specific and the processes in which they are used are normally very mild and 'green,' often enabling production methods that give reduced waste and a much lower environmental impact. However, the fact that these biocatalysts are often so specific for one reaction can be problematic when they are intended to be used to make valuable materials that are not found in Nature. To circumvent this problem, scientists have developed many methods to modify enzymes to improve characteristics for use in these non-natural reactions. This practice, called enzyme engineering, gives researchers the opportunity to customize the biocatalyst to fit the process in which it will be used, and has become widely implemented within chemical and pharmaceutical companies as a means to use natural and renewable catalysts to produce non-natural materials using sustainable, cost-effective production methods.Due to the success of biocatalysts in large scale manufacturing, industries are continuously looking for ways to install biocatalytic processes, as well as for enzymes that catalyse desirable new reactions not available among known biocatalysts. These additions can lead to the development of new and better products and innovative methods to replace current chemical processes with an equivalent biocatalytic route. Working to contribute to this desired expansion, the research proposed here aims to develop a series of engineered enzymes that catalyse a synthetically valuable reaction not currently offered by known biocatalysts. The utility of these biocatalysts will be demonstrated through the production of high-value chemicals found in pharmaceuticals and natural products. The goal is to provide a productive and environmentally friendly route for manufacturing a variety of chemical building blocks which will facilitate research toward determining and advancing their potential in medical applications. In order to accomplish this, we will establish a new biocatalytic strategy to make these compounds through the use of a novel biocatalyst, and apply enzyme engineering methods to quickly optimize its activity. The development of biological cost-effective and clean production methods will also be a hugely beneficial resource for future production of medicines and materials containing these valuable intermediates, helping ensure that these products can be globally available and environmentally sustainable.