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.

食品、清洁材料和个人护理产品等各种家用产品都依赖于工业规模改性起始材料来生产具有所需性能的产品的能力。在许多情况下，一个关键要求是引入带电基团，以赋予所需的特性，例如凝胶能力、结合其他材料或充当洗涤剂。这通常可以通过添加带电基团来实现，实现这一点的一个关键方法是添加硫酸基团。问题是目前这是使用有毒且破坏环境的化学品来完成的。全球此类家居产品市场巨大且不断增长，例如个人护理产品市场规模达73.5亿美元，年增长率为7%。我们的工业合作伙伴联合利华是全球主要参与者，拥有约 50% 的市场份额，与我们有着长期且良好的合作关系。 消费者对环境问题的敏感度，特别是现有的石油基产品和刺激性化学品的使用，由于它们在生产或处置过程中抗生物降解、产生温室气体和其他环境问题，最终导致了开发产品的商业压力可持续的替代品。目前工业上实现硫酸盐化的方法涉及选择性差且对环境有害的腐蚀性化学品，需要用一种使用可再生资源且不破坏环境的方法来取代。我们与联合利华一起致力于开发使用酶实现硫酸化的方法，从而避免这些问题。我们提出的路线 - 工程酶来进行这种修饰 - 不仅可以更好地控制过程，而且最重要的是，可以实现对环境负责的可生物降解产品和废物的生产。到目前为止，酶在这些领域的应用一直受到容易检测已进行的修饰的问题的阻碍，并且由于所涉及的一些材料的成本，还阻碍了开发商业上可行的添加硫酸基团的方法。然而现在，通过我们和联合利华所做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已建立的专业知识来实现​​两个主要目标：（i）组装技术（称为高通量酶工程平台）来生产和优化适合的酶适用于工业相关的各种酶驱动过程，(ii) 说明如何使用该平台来选择和优化合适的酶，使用一类可以将硫酸基添加到天然存在和可再生起始原料中的酶复合糖等材料来自植物的（多糖）和脂质（糖脂）。然后，联合利华将评估这些硫酸盐产品的工业应用潜力，联合利华是一家全球性大公司，制定了可持续发展议程，未来将能够提供清洁、可再生的产品。

项目成果

Dock-and-lock binding of SxIP ligands is required for stable and selective EB1 interactions

SxIP 配体的对接锁结合是稳定和选择性 EB1 相互作用所必需的

• DOI: 10.1101/2024.02.27.581919
• 发表时间: 2024-02-29
• 期刊: bioRxiv
• 作者: Teresa Almeida;Eleanor Hargreaves;Tobias Zech;Igor Barsukov
• 通讯作者: Igor Barsukov

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: http://dx.10.26434/chemrxiv-2021-4ftrg
• 发表时间: 2021
• 作者: Wheeler S

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

磷酸化和硫酸化具有共同的生物合成途径，但以不同的方式扩展了生物大分子的生化和进化多样性。

• DOI: http://dx.10.1098/rsif.2022.0391
• 发表时间: 2022
• 期刊: Journal of the Royal Society, Interface
• 作者: Lima MA

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: http://dx.10.33774/chemrxiv-2021-4ftrg
• 发表时间: 2021
• 作者: Wheeler S

Synthesis and toxicity profile in 293 human embryonic kidney cells of the ß D-glucuronide derivatives of ortho-, meta- and para-cresol.

邻甲酚、间甲酚和对甲酚的 D-葡萄糖醛酸衍生物在 293 个人胚胎肾细胞中的合成和毒性特征。

• DOI: http://dx.10.1016/j.carres.2020.108225
• 发表时间: 2021
• 期刊: Carbohydrate research
• 影响因子: 3.1
• 作者: London JA