(BBSRC DTP) Development of novel biocatalysts for the synthesis of alkaloids via ‘imine’ and ‘iminium ion’ catalysis

The alkaloids are a diverse family of nitrogen-containing natural products that have been shown to possess exquisite biological activity and hence have provided inspiration for the development of novel pharmaceuticals, agrochemicals and other biologically active molecules. Amongst the most well-known members of this class of natural products are compounds such as morphine (pain relief), nicotine (stimulant) and coniine (poison found in hemlock). In Nature these alkaloids are produced mainly in plants, via biosynthetic pathways which usually start with simple amino acids (e.g. lysine, tryptophan) and importantly involve the generation of imines or iminium ions as reactive intermediates. These biosynthetic pathways are remarkable in that relatively simple enzyme-catalysed transformations are used to build up complex molecules without the use of protecting groups. These pathways therefore provide inspiration for synthetic organic chemists wishing to create new efficient routes to alkaloid type molecules.

The goal of this cross-disciplinary project is to (i) generate a “toolbox” of engineered biocatalysts that are either able to generate imines/imines ions from the corresponding amines or alternatively convert imines/iminium ions to amines and other more functionalised molecules and (ii) develop synthetic approaches for the synthesis of specific imine/iminium ions which can act as novel substrates for these biocatalysts and which will ultimately lead to novel synthetic routes to natural and unnatural products possessing biological activity. In order to achieve these objectives it will be necessary to develop advanced tools for high-throughput screening, including those based upon mass spectrometry and mass spectroscopy, so that the desired biocatalysts can be engineered in order that they possess the required levels of activity and specificity.

The student will be trained in broad aspects of industrial biotechnology and biocatalysis, including microbial gene expression regulation, preparative biocatalysis, directed evolution, microbial fermentation, molecular biology and bio-analytical methods such GC-MS. The student will also gain expertise in ‘state of the art’ synthetic chemistry techniques, modern methods of product purification and spectroscopic data acquisition and analysis. The high-throughput screening aspects of the project will involve learning aspects of modern mass spectrometry. This project would suit individuals interested in future careers in biotechnology, biocatalysis, biological chemistry and bioprocessing.

http://www.manchester.ac.uk/research/nicholas.turner/
http://www.manchester.ac.uk/research/roger.whitehead/personaldetails


Contact for further Information
For more details contact Professor N Turner ([Email Address Removed])