Development of a biotechnology platform for enzymatic sulfation of industrial products based on polysaccharide sulfotransferases

基于多糖磺基转移酶的工业产品酶促硫酸化生物技术平台的开发

• 批准号: BB/V003372/1
• 负责人: Igor Barsukov
• 金额: $ 32.16万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV003372%2F1
• 关键词: Development; biotechnology; platform; enzymatic; sulfation

A wide range of household products as diverse as foodstuffs, cleaning materials and personal care products, rely on the ability to modify starting materials on an industrial scale to generate products with the desired properties. One key requirement in many cases is the introduction of charged groups, to bestow the desired characteristics such as the ability to gel, to bind other materials or to behave as detergents. This can often be achieved by the addition of charged groups and one key way to do this is to add a sulfate group. The problem is that this is done currently using toxic and environmentally damaging chemicals. The global market for such household products is huge and growing, for example, for personal care products is $ 7.35 Bn with annual growth of 7%. Our industrial collaborator, Unilever, with whom we have a long and well-established working relationship, is a major global player, with around 50% of the market share. Consumer sensitivity to environmental concerns, particularly with existing petroleum-based products and the use of harsh chemicals, arising from their resistance to biological degradation, the generation of greenhouse gases and other environmental issues during their production or disposal, has culminated in commercial pressure to develop sustainable alternatives.The current method of achieving sulfation industrially, involving aggressive chemicals which show poor selectivity and are environmentally damaging, needs to be replaced with a one employing renewable resources without damaging the environment. Together with Unilever, we aim to develop methods by which sulfation can be achieved using enzymes, thereby avoiding these problems. The route we propose - engineering enzymes to carry out this modification - offers both better control of the process and, crucially, enables environmentally responsible production of biodegradable products and waste. Until now, the application of enzymes to these areas has been hindered by the problems of readily detecting the modifications that have been made and, owing to the cost of some of the materials involved, also of developing a commercially feasible method of adding sulfate groups. Now, however, as a result the combination of preliminary work carried out by ourselves and Unilever, as well as other technological advances, both of these problems can be solved. This project will exploit these improved technologies, together with our established expertise in enzyme production to achieve two principal aims: (i) to assemble the technology (termed the high throughput enzyme-engineering platform) with which to produce and optimise enzymes that will be suitable for application to a wide range of enzyme-driven processes of industrial relevance and, (ii) to illustrate the use of this platform to select and optimise suitable enzymes, using a class of enzymes that can add sulfate groups to naturally-occurring and renewable starting materials such as complex sugars (polysaccharides) and lipids (glycolipids) from plants. The potential for industrial application of these sulfated products will then be assessed by Unilever, a major global company with a developed sustainability agenda that, in the future, will enable delivery of clean, renewable products.

各种各样的家用产品，如食品、清洁材料和个人护理产品，都依赖于在工业规模上对原料进行改性的能力，以生产具有所需性能的产品。在许多情况下，一个关键的要求是引入带电基团，以赋予所需的特性，如凝胶的能力，结合其他材料或作为洗涤剂的行为。这通常可以通过添加带电基团来实现，而实现这一点的一个关键方法是添加硫酸盐基团。问题是，目前这是使用有毒和破坏环境的化学物质来完成的。这类家用产品的全球市场是巨大的，而且还在不断增长，例如，个人护理产品的市场规模为73.5亿美元，年增长率为7%。我们的工业合作伙伴联合利华与我们有着长期和良好的工作关系，是一家主要的全球参与者，拥有约50%的市场份额。消费者对环境问题的敏感性，特别是对现有的石油产品和使用刺激性化学品的敏感性，因其在生产或处置过程中对生物降解、温室气体的产生和其他环境问题的抵抗而达到顶峰，最终导致开发可持续替代品的商业压力。目前在工业上实现硫酸盐化的方法涉及表现出较差选择性和破坏环境的侵略性化学品，需要用一种在不破坏环境的情况下利用可再生资源的方法来取代。与联合利华一起，我们的目标是开发使用酶实现硫酸盐化的方法，从而避免这些问题。我们提出的方法--设计酶来进行这种修饰--既提供了对过程的更好控制，而且至关重要的是，能够对环境负责地生产可生物降解产品和废物。到目前为止，酶在这些领域的应用一直受到以下问题的阻碍：容易检测所做的修饰，以及由于所涉及的一些材料的成本，也由于开发商业上可行的添加硫酸盐基团的方法。然而，现在，由于我们和联合利华进行的前期工作以及其他技术进步的结合，这两个问题都可以得到解决。该项目将利用这些改进的技术，以及我们在酶生产方面的成熟专业知识，以实现两个主要目标：(I)组装技术(称为高通量酶工程平台)，利用该技术生产和优化适用于广泛的工业相关酶驱动过程的酶，以及(Ii)说明使用该平台来选择和优化合适的酶，使用一类可以在天然产生的和可再生的起始材料中添加硫酸盐基团的酶，如来自植物的复合糖(多糖)和脂(糖脂)。这些硫酸盐产品的工业应用潜力将由联合利华评估，联合利华是一家大型全球公司，拥有制定的可持续发展议程，未来将能够交付清洁、可再生的产品。

项目成果

Anion binding to a cationic europium(III) probe enables the first real-time assay of heparan sulfotransferase activity

阴离子与阳离子铕 (III) 探针的结合首次实现了乙酰肝素磺基转移酶活性的实时测定

• DOI: 10.33774/chemrxiv-2021-4ftrg
• 发表时间: 2021
• 作者: Wheeler S

Exploration of expanded carbohydrate chemical space to access biological activity using microwave-induced acid condensation of simple sugars.

• DOI: 10.1039/d2ra01463g
• 发表时间: 2022-04-07
• 期刊: RSC advances
• 影响因子: 3.9
• 作者: London JA;Taylor SL;Barsukov I;Cartmell A;Yates EA
• 通讯作者: Yates EA

Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways.

• DOI: 10.1098/rsif.2022.0391
• 发表时间: 2022-08
• 期刊: Journal of the Royal Society, Interface

Anion binding to a cationic europium(III) probe enables the first real-time assay of heparan sulfotransferase activity.

• DOI: 10.1039/d1ob02071d
• 发表时间: 2022-01-19
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Wheeler S;Breen C;Li Y;Hewitt SH;Robertson E;Yates EA;Barsukov IL;Fernig DG;Butler SJ
• 通讯作者: Butler SJ