Industrial scale production of cyanobactin enzymes for fast and efficient cyclic peptide synthesis

工业规模生产蓝菌素酶，用于快速高效的环肽合成

• 批准号: BB/M013669/1
• 负责人: Marcel Jaspars
• 金额: $ 18.58万
• 依托单位: University of Aberdeen
• 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%2FM013669%2F1
• 关键词: Industrial; scale; production; cyanobactin; enzymes

The pharmaceutical industry needs cleaner and greener ways to produce complex compounds that will form the basis of future pharmaceuticals. In this project we will use enzymatic methods to generate cyclic compounds which may be applied as potential treatments for a range of diseases (e.g. fungal infection, epilepsy). The enzymes are derived from a marine blue-green alga and have been modified to make them more efficient. Combining these enzymes enables us to generate the compounds of interest in a few days compared to chemical synthesis which may take months. One aim of this project is to optimise the production of these enzymes with industry input, as well as streamline the whole process, including practical purification procedures. A key aim is to generate some compounds in reasonable quantity for testing against a number of disease models. Using this process we anticipate starting a company based around the ability to generate these unique cyclic compounds in a sustainable way.

制药行业需要更清洁、更环保的方法来生产复杂的化合物，这些化合物将成为未来制药的基础。在这个项目中，我们将使用酶的方法来产生环状化合物，这些环状化合物可以作为一系列疾病（例如真菌感染，癫痫）的潜在治疗方法。这些酶来自一种海洋蓝绿色植物，经过修饰使其更有效。结合这些酶使我们能够在几天内产生感兴趣的化合物，而化学合成可能需要数月。该项目的一个目的是优化这些酶的生产，并简化整个过程，包括实际的纯化程序。一个关键目标是以合理的数量产生一些化合物，用于对许多疾病模型进行测试。利用这一过程，我们预计将以可持续的方式创建一家公司，以生产这些独特的环状化合物。

项目成果

Structural analysis of leader peptide binding enables leader-free cyanobactin processing.

• DOI: 10.1038/nchembio.1841
• 发表时间: 2015-08
• 期刊: Nature chemical biology
• 影响因子: 14.8
• 作者: Koehnke J;Mann G;Bent AF;Ludewig H;Shirran S;Botting C;Lebl T;Houssen W;Jaspars M;Naismith JH
• 通讯作者: Naismith JH

A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway.

来自川单肽生物合成途径的独特的色氨酸C-丙基转移酶。

• DOI: 10.1002/anie.201509920
• 发表时间: 2016-03-07
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Parajuli, Anirudra;Kwak, Daniel H.;Dalponte, Luca;Leikoski, Niina;Galica, Tomas;Umeobika, Ugochukwu;Trembleau, Laurent;Bent, Andrew;Sivonen, Kaarina;Wahlsten, Matti;Wang, Hao;Rizzi, Ermanno;De Bellis, Gianluca;Naismith, James;Jaspars, Marcel;Liu, Xinyu;Houssen, Wael;Fewer, David Peter
• 通讯作者: Fewer, David Peter

N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway

• DOI: 10.1021/acs.biochem.8b00879
• 发表时间: 2018-12-18
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Dalponte, Luca;Parajuli, Anirudra;Fewer, David P.
• 通讯作者: Fewer, David P.