Glycoenzymes for Bioindustries

用于生物工业的糖酶

• 批准号: BB/M029034/1
• 负责人: Sabine Flitsch
• 金额: $ 158.42万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM029034%2F1
• 关键词: Glycoenzymes; Bioindustries

There are a wealth of glycoenzymes in nature but only a small number of enzymatic activities are used in industrial processes, primarily carbohydrate degrading enzymes used in high volume manufacturing such as amylases/xylanases/cellulases/oxidases used in baking/detergents/biofuels. Even fewer examples exist in high value manufacturing applications such as biologics: one example is the production of the therapeutic Cerezyme where alpha-neauramindase is used to deglycosylate exposing terminal Man residues improving its targeting. A major hurdle is the availability of appropriate enzymes which can limit utilisation in the early stage of process development thus reducing the number of successful processes involving glycoenzymes. The present project aims to overcome the current limitations of glycoenzyme availability by bringing together a number of innovative high-throughput approaches to biocatalyst discovery. We have assembled a list of 20 different glycoenzyme activities including various glycosyltransferases, polysaccharide-modifying enzymes, glycosidases and sugar oxidases that will form the basis of the research. Through iterative rounds of biocatalyst discovery, characterisation and development we aim to bring to market panels of different glycoenzyme classes that are readily available for screening by end users.

在自然界中存在丰富的糖酶，但在工业过程中仅使用少量的酶活性，主要是用于大批量制造的碳水化合物降解酶，例如用于烘焙/洗涤剂/生物燃料的淀粉酶/木聚糖酶/纤维素酶/氧化酶。在高价值制造应用（例如生物制剂）中存在的实例甚至更少：一个实例是治疗性Cerezyme的生产，其中α-新氨基酶用于去糖基化暴露末端Man残基，从而改善其靶向。一个主要的障碍是合适的酶的可用性，这可能限制在工艺开发的早期阶段的利用，从而减少涉及糖酶的成功工艺的数量。本项目旨在通过汇集一些创新的高通量方法来发现生物催化剂，以克服目前糖酶可用性的局限性。我们已经收集了20种不同的糖酶活性的列表，包括各种糖基转移酶，多糖修饰酶，糖苷酶和糖氧化酶，这些酶将构成研究的基础。通过一轮又一轮的生物催化剂发现、表征和开发，我们的目标是将不同糖酶类别的面板推向市场，这些面板随时可供最终用户筛选。

项目成果

Constructing Biocatalytic Cascades: In Vitro and in Vivo Approaches to de Novo Multi-Enzyme Pathways

• DOI: 10.1021/acscatal.6b02979
• 发表时间: 2017-01-01
• 期刊: ACS CATALYSIS
• 影响因子: 12.9
• 作者: France, Scott P.;Hepworth, Lorna J.;Flitsch, Sabine L.
• 通讯作者: Flitsch, Sabine L.

Innentitelbild: An Enzymatic N-Acylation Step Enables the Biocatalytic Synthesis of Unnatural Sialosides (Angew. Chem. 13/2020)

Innentitelbild：酶促 N-酰化步骤可实现非天然唾液酸苷的生物催化合成 (Angew. Chem. 13/2020)

• DOI: 10.1002/ange.202000641
• 发表时间: 2020
• 期刊: Angewandte Chemie
• 作者: Laborda P

Development and application of a highly a2,6-selective pseudosialidase

高α2,6-选择性假唾液酸酶的开发及应用

• DOI: 10.26434/chemrxiv.5336125.v1
• 发表时间: 2017
• 作者: Both P

The self-sufficient P450 RhF expressed in a whole cell system selectively catalyses the 5-hydroxylation of diclofenac.

• DOI: 10.1002/biot.201600520
• 发表时间: 2017
• 期刊: Biotechnology journal
• 影响因子: 4.7
• 作者: J. Klenk;B. Nebel;Joanne L Porter;Justyna K. Kulig;S. A. Hussain;Sven M. Richter;Michele Tavanti