How Nature builds the pigments of life
Vitamin B12 (1) is the anti-pernicious anaemia vitamin and the coenzyme form is used by several different enzymes to bring about remarkable rearrangements in living systems. The lecture will focus on the question "How is vitamin B12 biosynthesised". A very brief historical survey of what had been achieved earlier will be followed by a full account of the latest exciting advances. One take-home message is that any chemist aiming to solve the biosynthesis of a complex natural product must embrace genetics, molecular biology and enzymology whilst the biologists need the complementary strengths of the most advanced chemistry. A second theme will be to demonstrate the power of experiments, based on multiple labelling of biosynthetically generated intermediates, for studying natural pathways. The lecture will describe research involving molecular biology, enzymology, synthesis, isotopic labelling and the full panoply of modern NMR techniques. A family of coloured molecules including haem, chlorophyll, the cytochromes and vitamin B 12 are of such vital importance for living systems that they have become known as the Pigments of Life. The present lecture will focus on just one member, the anti-pernicious anaemia agent, vitamin B12 (1). It has a structure of considerable complexity and is often referred to as the Everest of biosynthetic problems. The question of how this structure is built in Nature has excited my group since we started on this problem in 1968 and happily much has been discovered about the biosynthetic pathway. I shall first outline very briefly what knowledge was available about those parts of the pathway which had been elucidated before 1990. Time does not allow this to be complete nor to include much detail; just the essential minimum information will be given to allow the reader to understand and enjoy the latest exciting developments. Full information and literature references are given in various reviews. (ref. 1).