Sustainable Biocatalytic Approaches to Pyridine and Piperidine Heterocycles

目前，用于制造塑料、药品和农用化学品的化学品和溶剂主要来自原油。随着我们寻求在21世纪创造一个更可持续的世界，我们的社会需要大幅减少对原油的依赖，这意味着要找到新的、可持续的方法来制造原料化学品。吡啶和哌啶是药物中常见的六元杂环，目前还没有可持续的路线来取代吡啶和哌啶。布格教授的研究小组发现，利用工程红球菌RHA1，从植物生物质中发现的聚合木质素可以生物转化为吡啶-二元酸。这项提议旨在扩大这一路线，以生产一系列可能成为有价值的原料化学品的取代吡啶。进一步的生物转化能够还原取代的吡啶，生成相应的饱和吡啶。因此，我们的目标是利用这种生物转化从相同的路线产生取代的哌啶类化合物。我们还将研究在Jostii红球菌RHA1中负责制造吡啶环的酶。这项研究将引起制药业工艺开发科学家的极大兴趣，我们将与阿斯特拉捷利康制药公司合作，进一步开发这项技术。

At present the chemicals and solvents used to make plastics, pharmaceuticals and agrochemicals are derived primarily from crude oil. As we seek to create a more sustainable world in the 21st century, our society needs to dramatically reduce its dependence upon crude oil, which means finding new, sustainable routes to make feedstock chemicals. Pyridines and piperidines are 6-membered heterocyclic rings that are commonly found in pharmaceutical drugs, and at present there is no sustainable route to substituted pyridines and piperidines. Prof Bugg's research group has discovered a biotransformation to pyridine-dicarboxylic acids from polymeric lignin found in plant biomass, using engineered Rhodococcus jostii RHA1. This proposal aims to expand this route to make a range of substituted pyridines that could be valuable feedstock chemicals. A further biotransformation is able to reduce substituted pyridines to make the corresponding saturated piperidines. We will therefore aim to use this biotransformation to generate substituted piperidines from the same route. We will also investigate the enzymes that are responsible for making the pyridine ring in Rhodococcus jostii RHA1. This research will be of considerable interest to process development scientists in the pharmaceutical industry, and we will collaborate with Astra Zeneca Pharmaceuticals to further develop this technology.