page_title: Alan R. Battersby
section_title: Biosynthesis of the "Pigments of Life"
hierarchical_section_title: Alan R. Battersby / Research / Biosynthesis of the "Pigments of Life"
caption_attribution_description: English: Prof Alan Battersby lecturing on porphyrin biosynthesis
context_page_description: Sir Alan Rushton Battersby FRS was an English organic chemist best known for his work to define the chemical intermediates in the biosynthetic pathway to vitamin B12 and the reaction mechanisms of the enzymes involved. His research group was also notable for its synthesis of radiolabelled precursors to study alkaloid biosynthesis and the stereochemistry of enzymic reactions. He won numerous awards including the Royal Medal in 1984 and the Copley Medal in 2000. He was knighted in the 1992 New Year Honours. Battersby died in February 2018 at the age of 92.
context_section_description: Alan Battersby is, above all, known for his research on the biosynthesis of the "pigments of life" that are built on closely related tetrapyrrolic structural frameworks. His research group elucidated, in particular, the essential role played by two enzymes, deaminase and cosynthetase, in the steps from aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III. The latter is the first macrocyclic intermediate in the biosynthesis of haem, chlorophyll, vitamin B₁₂ (cobalamin), sirohaem and cofactor F430. The work involved the careful study of labelled intermediates, using deuterium, tritium, ¹³C and ¹⁴C placed into potential precursors made by organic or enzyme-assisted synthesis. The most successful strategy was to incorporate the stable isotope ¹³C into potential substrates, since the outcome of the biochemical reactions (for example giving uroporphyrinogen III) could readily be followed using high-field ¹³C NMR. The Battersby group's use of doubly-¹³C-labelled porphobilinogen was especially revealing of the rearrangement step which had puzzled those who wished to understand the details of the biosynthesis of uroporphyrinogen III. Based on these results, Alan Battersby suggested that a spiro-pyrrolenine intermediate was generated at the active site of cosynthetase and to prove this mechanism his group designed and synthesised a spiro-lactam analogue which was indeed shown to inhibit the enzyme.
  Later steps towards vitamin B₁₂, especially the incorporation of the additional methyl groups of its structure, were investigated using methyl-labelled S-adenosyl methionine. It was not until a genetically-engineered strain of Pseudomonas denitrificans was used, in which eight of the genes involved in the biosynthesis of cobalamin had been overexpressed, that the complete sequence of methylation and other steps could be determined thus fully establishing all the intermediates in the pathway.
  As Alan Battersby wrote in his review article in Accounts of Chemical Research
  "One can get some appreciation of the massive effort that was involved by the groups of Arigoni, Battersby, Francis Blanche, Vladimir Bykhovski, Joel Crouzet,  Gerhard Muller and A. Ian Scott; K. Bernhauer and David Shemin also made some early contributions."
caption: Prof Alan Battersby lecturing on porphyrin biosynthesis.
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