Alan R. Battersby

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Cambridge University
ThesisResearches into the structure of Emetine (1949)
Doctoral advisorDr Hal T Openshaw
Doctoral studentsAndrew D. Hamilton
Craig Hawker

Sir Alan Rushton Battersby

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.[1]

Early life and education

Alan Battersby was born in

Second World War was underway and he decided that he should join the war effort by working for BICC in their local factory. He soon concluded that this decision had been a mistake and so used his spare time to study independently at Salford Technical College for the Higher School Certificate that would be required to enter university.[2][3][4]
In October 1943, Battersby took up his place at the
University of Illinois, working with Herbert Carter on pyruvate oxidation factor.[6][7][a]

Later career

In 1954, Battersby was appointed a lecturer at the University of Bristol, where he stayed until 1962. This was the period when his own research group of doctoral and post-doctoral students became established. In 1962 he was appointed as a professor of chemistry at

department and held that post until his retirement in 1992 when he was granted emeritus status within his college and department, reflecting his distinguished service.[6][7][8]

Research

The full output of Battersby's work has been published in over 350, mainly

Finian Leeper.[10]
The group was funded by external grants, including those from the
Hoffman-La Roche, the Wolfson Foundation and Zeneca.[10]

Alkaloids

chemical degradation and partial or complete synthesis of possible structures, was necessary to determine their chemical identity which, owing to their stereochemistry, was often difficult to fully describe.[11] This, for example, was the case for emetine, used for the treatment of amoebic infections and the subject of Battersby's PhD thesis.[5] As he later commented[7]

"Roughly 100 g of emetine had been consumed in this work; modern tools would allow the structure of emetine to be determined in three days at most using about 10 mg of recoverable material (365 times faster using 10,000 times less material)."

These tools are the now-familiar

anti-malarial drug was shown to derive from corynantheal, although it does not share its indole substructure.[7]

Biosynthesis of the "Pigments of Life"

Prof Alan Battersby lecturing on porphyrin biosynthesis.

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.[18][19] Based on these results, 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.[20]

Cambridge department
.

Later steps towards vitamin B12, especially the incorporation of the additional methyl groups of its structure, were investigated using methyl-labelled

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.[7][21]
[22] [23] As Battersby wrote in his review article in Accounts of Chemical Research[24]

"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."

Haem natural products and mimics

chemistry department
.

The Battersby group's work on the biosynthesis of haem-related

haem a,[25] haem d1[26] and sirohydrochlorin.[27] Another challenge requiring pure synthesis was to investigate the function of the enzymes that contained porphyrin-related ligands, or (in the case of haemoglobin) used haem for oxygen-transport, by mimicking these properties without recourse to the protein that in nature surrounds the active site. Battersby chose to investigate mimics for myoglobin and cytochrome P450, designing artificial targets wherein a single metal-containing coordination complex was synthesised and its behaviour compared with the natural system it was replacing. The small-molecule targets were porphyrins carrying substituents in positions where they would be unlikely to interfere with the electronic properties of the metal complex. By the time that he retired in 1992, this area of chemistry had become very active.[28]
[29]

Stereochemistry of enzymic reactions

The work described above is a subset of a broader field which attempts to understand the stereochemistry and mechanism of enzyme catalysis. The Battersby group used their expertise in the use of tritium-labelled substrates to probe a number of enzyme systems, for example histidine decarboxylase and tyrosine decarboxylase.[15]

Personal life

Battersby married Margaret Ruth née Hart in 1949. She was a

fly-fishing but he also kept in touch with his many colleagues and former students.[3][4][30]

Honours and awards

Battersby received

Liverpool University in 1994.[35]
In 1988, he was elected a Foreign Honorary Member of the American Academy of Arts and Sciences,[36] and a Foreign Fellow of the National Academy of Sciences of India in 1990. He was awarded the Wolf Prize in Chemistry along with Duilio Arigoni of ETH Zurich in 1989 for "their fundamental contributions to the elucidation of the mechanism of enzymic reactions and of the biosynthesis of natural products, in particular the pigments of life".[37]

The Award of the Copley Medal of the Royal Society was made:

In recognition of his pioneering work in elucidating the detailed biosynthetic pathways to all the major families of plant alkaloids. His approach, which stands as a paradigm for future biosynthetic studies on complex molecules, combines isolation work, structure determination, synthesis, isotopic labelling and spectroscopy, especially advanced NMR, as well as genetics and molecular biology. This spectacular research revealed the entire pathway to vitamin B12.[43]

References

Notes

  1. ^ Reference [7] is, in effect, Sir Alan Battersby's autobiography. Initially drafted in 2002 for a departmental symposium, it provides a candid account of his scientific journey from childhood to old age. The expanded book chapter published in 2005 was "written for the non-specialist audience" and includes many insights into the choices and decisions he made, for example to switch from alkaloid chemistry to the "pigments of life".

References

  1. ^ "Professor Sir Alan Battersby (1925-2018)". St Catharine's College, Cambridge. Retrieved 1 May 2018.
  2. ^
    ISBN 978-0-19-861412-8
    .
  3. ^ a b c "Sir Alan Battersby's 90th Birthday Celebrations". St Catharine's College, Cambridge. 21 March 2015. Retrieved 1 May 2018.
  4. ^ a b "Battersby's obituary in The Times newspaper". The Times. 3 February 2018. Retrieved 1 May 2018.
  5. ^
    hdl:10023/11240
    .
  6. ^
    PMID 23963504. Archived from the original
    on 11 May 2018. Retrieved 1 May 2018.
  7. ^
    ISBN 0-521-82873-2
    .
  8. Department of Chemistry, University of Cambridge
    . Retrieved 1 May 2018.
  9. ^ "Alan Rushton Battersby publications". Academictree.org. Retrieved 21 July 2020.
  10. ^ a b "Google Scholar results for A R Battersby".
  11. ISBN 978-1-4832-2197-7
    .
  12. doi:10.1002/jlac.19375300116
    .
  13. doi:10.1016/S0021-9258(18)56441-3
    .
  14. PMID 14288334
    .
  15. ^
    doi:10.1021/ar50052a005
    .
  16. ^ "Battersby group papers about colchicine".
  17. PMID 11245400
    .
  18. S2CID 9070849
    .
  19. PMID 16042604
    .
  20. doi:10.1039/P19930002875
    .
  21. ^
    S2CID 2022475
    .
  22. S2CID 83942303
    .
  23. PMID 11152419
    .
  24. doi:10.1021/ar00025a003
    .
  25. doi:10.1039/P19850000135
    .
  26. doi:10.1039/A700655A
    .
  27. doi:10.1039/C39850001061
    .
  28. ISBN 978-3-540-17531-5
    .
  29. ISBN 978-3-540-12821-2
    .
  30. Department of Chemistry, University of Cambridge
    . Retrieved 20 May 2018.
  31. ^ "Masterlist - Honorary Graduates 1921-2012" (PDF). www.st-andrews.ac.uk. Archived from the original (PDF) on 5 March 2016. Retrieved 1 May 2018.
  32. ^ "Honorary Graduates" (PDF). www.sheffield.ac.uk. Archived from the original (PDF) on 29 October 2013. Retrieved 1 May 2018.
  33. ^ "Heriot-Watt University Edinburgh: Honorary Graduates" (PDF). www.hw.ac.uk. Retrieved 1 May 2018.
  34. ^ "Honorary Degrees". www.bristol.ac.uk. Archived from the original on 19 April 2018. Retrieved 1 May 2018.
  35. ^ "Liverpool University Honorary Graduates" (PDF). www.liverpool.ac.uk. Archived from the original (PDF) on 20 February 2020. Retrieved 1 May 2018.
  36. ^ "Book of Members, 1780-2010: Chapter B" (PDF). American Academy of Arts and Sciences. Retrieved 1 May 2018.
  37. ^ a b "The Wolf Prize in Chemistry". Wolf Foundation. Retrieved 1 May 2018.
  38. ^ "RSC Corday-Morgan Prize Previous Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  39. ^ "RSC Tilden Prize Previous Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  40. ^ "Battersby, Alan Rushton - Certificate of election as Fellow of the Royal Society". The Royal Society. Archived from the original on 8 July 2019. Retrieved 11 May 2018.
  41. ^ "Hugo Müller Lectureship Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  42. ^ "Flintoff Medal Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  43. ^ a b c d "Alan Battersby's Biography on The Royal Society website". The Royal Society. Archived from the original on 18 January 2021. Retrieved 17 February 2023.
  44. ^ "Recipients of Paul Karrer Gold Medal". University of Zurich. Retrieved 1 May 2018.
  45. ^ "Max Tishler Prize Lecturers". Harvard University. Retrieved 1 May 2018.
  46. ^ "Natural Product Chemistry Award Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  47. ^ "Pedler Award Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  48. ^ "Adams Award Winners". American Chemical Society Division of Organic Chemistry. Retrieved 1 May 2018.
  49. ^ "Havinga Foundation Laureates". Havinga Foundation.org. Retrieved 1 May 2018.
  50. ^ "Longstaff Prize Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  51. ^ "Robert Robinson Winners". Royal Society of Chemistry. Retrieved 1 May 2018.
  52. ^ "Antonio Feltrinelli Prizewinners". www.lincei.it. Archived from the original on 3 September 2012. Retrieved 1 May 2018.
  53. ^ "Tyler Distinguished Lecturers". Purdue University College of Pharmacy. Retrieved 1 May 2018.
  54. ^ "New Year's Honours List 1992". The London Gazette.
  55. ^ "August Wilhelm von Hofmann Prizewinners". Gesellschaft Deutscher Chemiker. Retrieved 1 May 2018.
  56. ^ "Levinstein Memorial Lecturers". Society of Chemical Industry. Retrieved 1 May 2018.
  57. ^ "Tetrahedron Prize Winners". Elsevier. Retrieved 1 May 2018.
  58. ^ "Inhoffen Medal Winners". Helmholtz Centre for Infection Research. Retrieved 1 May 2018.
  59. ^ "Welch Award Recipients". Welch1.org. Retrieved 1 May 2018.
  60. ^ "Robert Burns Woodward Career Award in Porphyrin Chemistry". Society of Porphyrins & Phthalocyanines. Retrieved 1 May 2018.

Further reading

External links
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