Nature generates amines (e.g. alkaloids, amino acids) via multienzyme biosynthetic pathways and in doing so creates some of the most complex natural products that have been discovered to date (e.g. morphine, vinblastine, reserpine). These biosynthetic pathways are truly remarkable in the way in which many enzymes are able to collectively process substrates in an orchestrated assembly line manner with no use of protecting groups and minimal side reactions. Despite our much deeper understanding of how these biosynthetic pathways operate, in terms of the substrates and enzymes involved, only recently have scientists begun to assemble these pathways in host systems for eventual scale-up and production of opiates.
Most synthetic amines are produced using abiological methods, particularly where cost and scale of operation are important. The majority of these chemical processes for amine production involve the use of high temperatures, pressures and expensive metal catalysts. In addition, the precursors for amine manufacture are largely derived from the petrochemical industry and hence are non-sustainable. Clearly a major challenge going forward is to try to recreate these cascade processes, both in vitro and in vivo, particularly for the production of non-natural synthetic amines.
The overall aim of the BIO-H-BORROW project is to develop a new biocatalytic approach for amine synthesis in which alcohols are used as universal substrates, ammonia is the source of the amine in the product, and the only by-product of the reaction is water. Initial work focused on characterisation and engineering of suitable enzymes and development of supporting analytical methodologies.
