The Bakerian lecture, 1984. Biosynthesis of the pigments of life

Many vitally important functions in living systems are carried out by metal ions held as complexes within organic ligands, the organic part of the molecule being a tetrapyrrolic macrocycle. Chlorophyll, haemoglobin, the cytochromes and vitamin B12 all fall into this family of 'pigments of life', a list that emphasizes their central importance in living systems. Research on the biosynthesis of these pigments has involved the synergistic combination of synthesis, structure determination, carbon nuclear magnetic resonance and isotopic labelling with radioactive and stable isotopes in conjunction with enzymology and kinetics. The lecture describes the logical series of experiments based on these approaches which have led to a step-by-step knowledge of the biosynthesis of the parent macrocycle (uroporphyrinogen-III) from which the other pigments are derived. One main pathway from the parent macrocycle involves oxidative transformations and leads eventually to protohaem required inter alia for haemoglobin and myoglobin. The second important pathway makes use of C-methylation to convert the parent macrocycle through many stages finally into vitamin B12. The biosynthetic studies on vitamin B12 are outlined with particular emphasis on the use of isotopic labelling with both radioactive and stable isotopes of carbon and hydrogen. Roughly two-thirds of the entire biosynthetic pathway to vitamin B12 has now been elucidated. The scarcity of several of the known intermediates on the pathway severely hampers future researches and progress towards the total synthesis of these key materials is reviewed. Finally, the lecture brings out the evolutionary interest of what has been discovered about the biosynthesis of the pigments of life.