17-ERACoBioTech Methyl Transferases for the Functional Diversification of Bioactives: BioDiMet

BioDiMet旨在实施Nature的策略，选择性地将目标化合物甲基化，作为一个强大的酶平台，准备在早期工业规模上使用。在自然界中，甲基化是由sam依赖的甲基转移酶进行的，这是完成和增强化合物生物活性的关键步骤。这些反应可以选择性地发生，这是很难用现有的化学合成方法来实现的，这些方法主要是使用有毒的甲基化剂，如碘化甲酯和硫酸二甲酯。酶法具有可持续性、避免使用有毒试剂和反应选择性等优点。这与制药、农用化学品和香料/香精行业数十亿英镑市场中开发新型生物活性物质的需求密切相关。尽管在自然界中很重要，但sam依赖的甲基转移酶在工业合成中完全没有得到充分利用。这主要是因为需要一种额外的化合物，一种辅助因子，称为s -腺苷型蛋氨酸（SAM）。这是非常昂贵的购买。为了克服这个问题，可以使用SAM辅助因素供应/回收系统，但目前还没有这些系统。此外，还需要一个强大的甲基转移酶工具箱。近年来，BioDiMet联盟的成员通过建立集成SAM辅助因子供应或回收的智能酶甲基化级联，证明了这些限制不再成立。BioDiMet现在是这些酶在工业上工业化的下一步。该项目将生产一个甲基转移酶工具箱，该工具箱对一系列化学结构具有活性，并使用SAM辅助因子供应或回收系统。它们将与其他酶一起使用，以产生对重要化合物类别的可持续反应级联。此外，我们将提高甲基转移酶的稳健性，使其能够在工业上使用。在项目范围内开发规模反应和下游处理方法也将促进平台技术的工业可行性。因此，BioDiMet将为通过强大的选择性生物催化甲基化合成新的生物活性提供工具，并具有通过化合物库甲基化开发新的活性药物成分的巨大潜力。甲基转移酶谱的开发有可能使我们获得大量以前无法获得的具有理想特性的多种生物活性物质，从而为工业提供新产品。

BioDiMet aims to implement Nature's strategy to selectively methylate target compounds as a robust enzymatic platform ready for use at an early industrial scale. In Nature methylation is performed by enzymes called SAM-dependent methyl transferases, and this is a key step to accomplish and enhance the bioactivity of compounds. The reactions can occur in a selective manner and this is very difficult to achieve using established chemical synthetic methods where mainly toxic methylation agents such as methyl iodide and dimethyl sulfate are used. Enzymatic approaches have the advantages of sustainability, the avoidance of such toxic reagents, and reaction selectivity. This is of great relevance to the need for the development of novel bioactives in multi-billion pound markets of the pharma, agrochemical and fragrance/flavour industries. Despite the importance in Nature, SAM-dependent methyl transferases are completely underexploited in industrial synthesis. This is mainly because an additional compound, a co-factor, is required known as S-adenosyl methionine (SAM). This is extremely expensive to purchase. To overcome this problem SAM co-factor supply/recycling systems can be used but these have not been available. In addition, a robust methyl transferase enzyme toolbox is needed. In recent years members of the BioDiMet consortium demonstrated that these limitations do not hold true anymore by establishing smart enzymatic methylation cascades with integrated SAM co-factor supply or recycling. BioDiMet is now the next step towards industrialisation of these enzymes in industry. The project will produce a toolbox of methyl transferases that are active towards a range of chemical structures and use SAM co-factor supply or recycling systems. They will be used with other enzymes to produce sustainable reaction cascades to important classes of compounds. In addition we will improve the robustness of the methyl transferases so they can be used by industry. Development of scaled-up reactions and down-stream processing methods within the project will also facilitate the industrial feasibility of the platform technology. BioDiMet will therefore provide tools to synthesize new bioactives through powerful selective biocatalytic methylation and holds significant potential to develop novel active pharmaceutical ingredients via the methylation of compound libraries. Development of a spectrum of methyl transferases potentially allows access to a plethora of previously unobtainable diverse bioactives with desirable properties to deliver new products for industry.