Professor Jake MacMillan, FRS
Foreign Associate of the National Academy of Science USA

Summary:

Publications on the chemistry and biochemistry of natural products, especially plant hormones, but including colchicine, the mitotic inhibitor; griseofulvin, the anti-mycotic fungicide; colletotrichin, the cytochrome inhibitor; wortmannin, the PI3-kinase inhibitor; colletodiol, a fungal macrocyclic dilactone; hevadride, a fungal nonadride; and fungal pigments, such as xanthomegin and its relatives.

Research Highlights:

Early research (see Ref. 1) comprised the isolation and determination of the structures of fungal metabolites of biological interest such as the anti-mycotic fungicide. griseofulvin (Ref. 2-4); the cytochrome inhibitor, colletotrichin (Ref. 5) ; the PI3-kinase inhibitor, wortmannin (Ref. 6-8); and gibberellic acid, initially as a plant growth promoter of fungal origin (Ref. 9). The structural studies on gibberellic acid led to the main interest - interdisciplinary studies on plant growth hormones, particularly the gibberellins.
Highlights include:

(i) the original isolation, and determination of the structures, of gibberellins from higher plants (Ref. 10-12);

(ii) an internationally accepted system for the assignment of trivial names (GA₁-GA_n) to gibberellins (Ref. 13);

(iii) the development of gas chromatography-mass spectrometry (GC-MS), together with real-time GC-MS data processing systems, for the identification, and quantification, of GAs (Ref. 14-19). These methods have shown the widespread occurrence of GAs in the plant kingdom (125 individual GAs are now known in plants, fungi and bacteria (Ref. 20);

(iv) synthesis of isotopically labelled substrates (Ref. 21-28) to determine the specific steps, and their stereochemistry, in the metabolic pathways of the GAs in the fungus, G. fujikuroi, (Ref. 29-33) and in higher plants, both in vitro, (Ref. 34-38, in collaboration with J.E. Graebe, and Ref 39), and in vivo in developing pea seed (Ref. 40-43) and in maize shoots (Ref. 44-47, in collaboration with B.O. Phinney). The use of mutants in the GA-biosynthetic pathway, in collaboration with B.O. Phinney, has been particularly rewarding and is reviewed in Ref. 48.

Other notable endeavours include: demonstration of the quantitative relationship between GA₁ and internode growth in Pisum sativum L. (Ref. 49); studies on the enzymes of the GA-biosynthetic pathway (Ref. 50-54); the preparation and use of epitope specific monoclonal antibodies to the GAs (Ref. 54- 60). There is also a recent review (Ref. 61) on diterpene biosynthesis.

Brief CV:

• D.Sc. (1968, University of Bristol)
• Ph.D. (1949, University of Glasgow)
• B.Sc. (1946, University of Glasgow).
• 1993- Senior Research Fellow, IACR-Long Ashton, Department of Agricultural Sciences, University of Bristol.
• 1990-1993 Post-doc., UCLA
• 1963-1990 Lecturer, Reader, Personal Chair, Head of Organic Chemistry, Chairman, School of Chemistry, University of Bristol.
• 1949-1962 Research Chemist, Section Leader, Akers Research Lab. Imperial Chemical Industries plc.
• 1962-1963 Associate Research Manager, Pharmaceuticals Division, Imperial Chemical Industries plc.

Distinctions:

• 1995 Pergamon Phytochemical Prize
• 1991 Foreign Associate of the US National Academy of Sciences.
• 1990 Wilson Baker Lecturer, University of Bristol
• 1989 Elected Honorary Member of the Botanical Society of America
• 1988-1989 Royal Society of Chemistry Hugo-Muller Lecturership and Medal
• 1988 Royal Society of Chemistry Award in Natural Product Chemistry
• 1988 American Society of Plant Physiology, Charles Reid Barnes Award
• 1987 Elected Distinguished Foreign Scholar of Mid-America Association of State Universities
• 1987 Elected Honorary Member of the Japanese Society for Chemical Regulation in Plants
• 1982 Research Medal, International Plant Growth Substance Association
• 1978 Elected Fellow of the Royal Society
• 1978 Elected Corresponding Member of the American Society of Plant Physiology
• 1978 Flintoff Medal, Royal Society of Chemistry
• 1973-1976 President of the International Plant Growth Substance Association.

Selected References

1. MacMillan, J. (1996) Reflections of a bio-organic chemist, Annu, Rev. Plant Physiol. Plant Mol. Biol., 47, 1-21.
2. Grove, J.F., MacMillan, J., Mulholland, T.P.C. and Rogers, M.A.T. (1952) Griseofulvin. Part IV. Structure. J. Chem. Soc. 3977-3987.
3. MacMillan, J. (1953) Griseofulvin. Part VII. Dechlorogriseofulvin. J. Chem. Soc. 1697-1702.
4. MacMillan, J. (1954) Griseofulvin. Part IX. Isolation of the bromo-analogue from Penicillium griseofulvum and Penicillium nigricans. J. Chem. Soc. 2585-2587.
5. Goddard, R., Hatton, I.K., Howard, J.A.K., MacMillan, J. and Gilmore, J.G. (1979) Fungal Products. Part 22. X-Ray and molecular structure of the mono-acetate of colletotrichin. J. Chem. Soc. Perkin Trans. I 1494-1498.
6. MacMillan, J., Vanstone, A.V. and Yeboah, S.K. (1972) Fungal Products. Part III. Structure of wortmannin and some hydrolysis products. J. Chem. Soc. (C) 2898-2903.
7. MacMillan, J., Simpson, T.J. and Yeboah, S.K. (1972) Absolute stereochemistry of the fungal product, wortmannin. J. Chem. Soc. Chem. Commun. 1063.
8. Simpson, T.J., Lunnon, M.W. and MacMillan, J. (1979) Fungal Products. Part 21. Biosynthesis of the fungal metabolite, wortmannin, from [1,2-13C2]-acetate and some hydrolysis products. J. Chem. Soc. Perkin Trans. I 931-934.
9. Cross, B.E., Grove, J.F., MacMillan, J., Moffatt, J.S., Mulholland, T.P.C., Seaton, J.C. and Sheppard, N. (1959) A revised structure for gibberellic acid. Proc. Chem. Soc. 302-303.
10. MacMillan, J. and Suter, P.J. (1958) The occurrence of gibberellin A₁ in higher plants: Isolation from the seed of runner bean (Phaseolus multiflorus). Naturwissenschaften 45, 46-47.
11. MacMillan, J., Seaton, J.C. and Suter, P.J. (1959) A new plant-growth promoting acid - gibberellin A₅ from the seed of Phaseolus multiflorus. Proc. Chem. Soc. 325.
12. MacMillan, J., Seaton, J.C. and Suter, P.J. (1962) Plant hormones-II. Isolation and structure of gibberellin A₆ and gibberellin A₈. Tetrahedron 18, 349-355.
13. MacMillan, J. and Takahashi, N. (1968) A proposed procedure for the allocation of trivial names to the gibberellins. Nature 217, 170-171.
14. Binks, R., MacMillan, J. and Pryce, R.J. (1969) Plant Hormones-VIII. Combined gas chromatography-mass spectrometry of the methyl esters of gibberellins A₁ to A₂₄ and their trimethylsilyl ethers. Phytochemistry 8, 271-284.
15. Binks, R., Cleaver, R.L., Littler, J.S. and MacMillan, J. (1971) Real time processing of low resolution mass spectra. Chemistry in Britain 7, 8-12.
16. Bowen, D.H., MacMillan, J. and Graebe, J.E. (1972) Determination of specific radioactivity of [¹⁴C]-compounds by mass spectrometry. Phytochemistry 11, 2253-2257.
17. Rivier, L., Gaskin, P., Albone, K.S. and MacMillan, J. (1981) GC-MS identification of endogenous gibberellins and gibberellin conjugates as their permethylated derivatives. Phytochemistry 20, 687-692.
18. Gaskin, P. and MacMillan, J. (1991) GC-MS of Gibberellins and Related Compounds: Methodology and a Library of Reference Spectra. University of Bristol, UK., Cantocks Enterprises Ltd, pp 519.
19. Croker, S.J., Gaskin, P., Hedden, P. MacMillan, J. and MacNeil, K.A.G. (1994) Quantitative analysis of gibberellins by isotope dilution mass spectrometry: A comparison of the use of calibration curves, an isotope dilution fit program and arithmetical correction of isotope ratios. Phytochemical Analysis 5, 74-80.
20. http://www.plant-hormones.info/gainplants/occurrence_of_gas_in_plants.htm;
    http://www.plant-hormones.info/gainplants/gasinfungi.htm;
    http://www.plant-hormones.info/gainplants/gasinbacteriai.htm
21. Beale, M.H., Gaskin, P., Kirkwood, P.S. and MacMillan, J. (1980) Partial synthesis of gibberellin A₉ and [3α- and 3β-2H1] gibberellin A₉ ; gibberellin A₅ and [1β -²H₂ and ³H₂] gibberellin A₅; and gibberellin A₂₀ and [1β,3α-²H₂ and-³H₂] gibberellin A₂₀. J. Chem. Soc. Perkin Trans. I 885-891.
22. MacMillan, J. and Willis, C.L. (1984) Stereoselective deuteriation at carbon-2 of the gibberellins. J. Chem. Soc. Perkin Trans. I., 357-361.
23. Albone, K.S., MacMillan, J., Pitt, A.R. and Willis, C.L. (1986) Isotopic labelling on ring A of gibberellin A₂₀. Tetrahedron 42, 3203-3214.
24. MacMillan, J. and Willis, C.L. (1986) Partial synthesis of [1β,2β-²H₂]-, [2β-²H]- and [2α-²H]gibberellin A₁. J. Chem. Soc. Perkin Trans. I 309-313.
25. Albone, K.S., MacMillan, J., Pitt, A.R. and Willis, C.L. (1986) Isotopic labelling on ring A of gibberellin A₂₀. Tetrahedron 42, 3203-3214.
26. MacMillan, J. and Willis, C.L. (1986) Partial synthesis of [1β,2β-²H₂]-, [2β-²H]- and [2α-²H]gibberellin A₁. J. Chem. Soc. Perkin Trans. I 309-313.
27. Willis, C.L., Gaskin, P. and MacMillan, J. (1988) [1β,2β,3β-³H₃]GA₂₀: Confirmation of structure by ³H NMR and by Mass Spectrometry. Phytochemistry 27, 3970-2.
28. Castellaro, S.J., Dolan, S.C., MacMillan, J. and Willis, C.L. (1990) Deuterium labelling of ent-kauren-19-oic acid at carbon-6 and-7. Phytochemistry 29, 1823-2831.
29. Bearder, J.R., MacMillan, J., Wels, C.M., Chaffey, M.B. and Phinney, B.O. (1974) Fungal Products. Part XI. Position of the metabolic block for gibberellin biosynthesis in the mutant B1-41a of Gibberella fujikuroi. Phytochemistry 13, 911-917.
30. Hedden, P., MacMillan, J. and Phinney,.B.O. (1974) Fungal Products. Part XII. Gibberellin A₁₄- aldehyde, an intermediate in gibberellin biosynthesis in Gibberella fujikuroi. J. Chem. Soc. Perkin Trans. I 587-592.
31. Bearder, J.R., MacMillan, J. and Phinney, B.O. (1975) Fungal Products. Part XIV. Metabolic pathways from ent-kaurenoic acid to the fungal gibberellins in mutant B1-41a of Gibberella fujikuroi. J. Chem. Soc. Perkin Trans. I 721-726.
32. Bearder, J.R., MacMillan, J. and Phinney. B.O. (1976) Origin of the oxygen atoms in the lactone bridge of C₁₉-gibberellins. J. Chem. Soc. Chem. Commun. 834-835.
33. Castellaro, S.J., Dolan, S.C., Hedden, P., Gaskin, P. and MacMillan, J. (1990) Stereochemistry of the metabolic steps from kaurenoic acids to kaurenolides and gibberellins. Phytochemistry 29, 1833-1839.
34. Graebe, J.E., Bowen, D.H. and MacMillan, J. (1972) The conversion of mevalonic acid into gibberellin A₁₂-aldehyde in a cell-free system from Cucrbita pepo. Planta 102, 261-271.
35. Graebe, J.E., Hedden, P., Gaskin, P. and MacMillan, J. (1974) The biosynthesis of a C₁₉-gibberellin from mevalonic acid in a cell-free system from a higher plant. Planta 120, 307-309.
36. Graebe, J.E., Hedden, P., Gaskin, P. and MacMillan, J. (1974) Biosynthesis of gibberellins A₁₂, A₁₅, A₂₄, A₃₆ and A₃₇ in a cell-free system from Cucurbita maxima. Phytochemistry 13, 1433-1440.
37. Ropers, H.-J., Graebe, J.E., Gaskin, P. and MacMillan, J. (1978) Gibberellin biosynthesis in a cell-free system from immature seeds of Pisum sativum. Biochem. Biophys. Res. Commun. 80, 690-697.
38. Hedden, P., Graebe, J.E., Beale, M.H., Gaskin, P. and MacMillan, J. (1984) The biosynthesis of 12α-hydroxylated gibberellins in a cell-free system from Cucurbita maxima. Phytochemistry 23, 569-574.
39. Albone, K.S., Gaskin, P., MacMillan, J., Phinney, B.O. and Willis, C.L. (1990) Biosynthetic origin of gibberellins A₃ and A₇ in cell-free preparations from seeds of Marah macrocarpus and Malus domestica. Plant Physiol. 94, 132-142.
40. Frydman, V.M. and MacMillan, J. (1975) The metabolism of gibberellins A₉, A₂₀ and A₂₉ in immature seed of Pisum sativum cv. Progress No. 9. Planta 125, 181-195.
41. Frydman, V.M. and MacMillan, J. (1977) Further studies on the metabolism of gibberellins (GAs) A₉, A₂₀ and A₂₉ in immature seed of Pisum sativum cv. Progress No. 9. Planta 135, 129-136.
42. Sponsel, V.M. and MacMillan, J. (1978) Metabolism of gibberellins A₂₉ in seed of Pisum sativum cv. Progress No. 9; use of [²H] and [³H]GAs, and the identification of a new GA catabolite. Planta 144, 69-78.
43. Sponsel, V.M. and MacMillan, J. (1980) Metabolism of [¹³C₁]gibberellins A₂₉ to [¹³C₁]gibberellin-catabolite in maturing seeds of Pisum sativum cv. Progress No. 9. Planta 150, 46-52.
44. Spray, C.R., Phinney, B.O., Gaskin, P., Gilmour, S.J. and MacMillan, J. (1984) Internode length in Zea mays L. The dwarf-1 mutation controls the 3β-hydroxylation of gibberellin A₂₀ to gibberellin A₁. Planta 160, 464-468.
45. Fujioka, S., Yamane, H., Spray, C.R., Phinney, B.O., Gaskin, P. MacMillan, J. and Takahashi, N. (1990) Gibberellin A₃ is biosynthesised from gibberellin A₂₀ via gibberellin A₅ in shoots of Zea mays L. Plant Physiol. 94, 127-131.
46. Kobayashi, M., Spray, C.R., Phinney, B.O., Gaskin, P. and MacMillan, J. (1996) Gibberellin metabolism in maize. The stepwise conversion of gibberellin A₁₂-aldehyde to gibberellin A₂₀, Plant Physiol., 110, 413-418.
47. Spray, C.R., Kobayashi, M., Suzuki, Y, Phinney, B.O., Gaskin, P. and MacMillan, J. (1996) The dwarf-1 (d1) mutation of Zea mays blocks three steps in the gibberellin biosynthetic pathway, Proc. Nat. Acad. Sci. USA, 93, 10515-10518.
48. MacMillan, J. (1997) Biosynthesis of the gibberellin plant hormones. Nat. Prod. Rep., 14, 221-243.
49. Ingram, T.J., Reid, J.B. and MacMillan, J. (1986) The quantitative relationship between gibberellin A₁ and internode growth in Pisum sativum L. Planta, 168, 414-420.
50. Smith, V.A. and MacMillan, J. (1984) Purification and partial purification of a gibberellin 2β-hydroxylase from Phaseolus vulgaris. J. Plant Growth Regul. 2, 251-254.
    
51. Albone, K., Gaskin, P., MacMillan, J., Smith, V.A. and Weir, J. (1989) Enzymes from seeds of Phaseolus vulgaris L.: Hydroxylation of gibberellin A₂₀ and gibberellin A₁ and 2,3-dehydrogenation of gibberellin A₂₀. Planta 177, 108-115.
52. Smith, V.A., Gaskin, P. and MacMillan, J. (1990) Partial purification and characterisation of the gibberellin A₂₀ 3β-hydroxylase from seeds of Phaseolus vulgaris. Plant Physiol. 94, 1390-1401.
53. Smith, V.A., Albone, K.S. and MacMillan, J. (1991) Enzymatic 3β-hydroxylation of gibberellins A₂₀ and A₅. in Gibberellins (ed Takahashi, N., B.O. Phinney and J. MacMillan) Springer-Verlag, New York Inc., 62-71.
54. MacMillan, J., Ward, D.A., Phillips, A.L., Sanchez-Beltran, Gaskin, P., Lange, T, and Hedden, P. (1997) Gibberellin biosynthesising ezymes in seeds of Marah macrocarpus: The isolation and expression of a carbon-20 oxidase, Plant Physiol., 113, 1369-1377.
55. Knox, J.P., Beale, M.H., Butcher, G.W. and MacMillan, J. (1987) Preparation and characterisation of monoclonal antibodies which recognise different gibberellin epitopes. Planta 170, 86-91.
56. Knox, J.P., Beale, M.H., Butcher, G.W. and MacMillan, J. (1988) Monoclonal antibodies to 13-deoxygibberellins. Plant Physiol. 88, 959-960.
57. Waycott, W., Smith, V.A., Gaskin, P., MacMillan, J. and Taiz, L. (1991) The endogenous gibberellins of dwarf mutants of lettuce. Plant Physiol. 95, 1169-1173.
58. Smith, V.A. and MacMillan, J. (1989) An immunological approach to gibberellin purification and quantification. Plant Physiol. 90, 1148-1155.
59. Nester-Hudson, J.E., Beale, M.H. and MacMillan, J. (1992) Large scale purification and preliminary structural studies of MAC 182, a gibberellin-binding monoclonal antibody. Phytochemistry 31, 3337-3339.
60. Smith, V.A., Sponsel, V.M., Knatt, C., Gaskin, P. and MacMillan, J. (1991) Immunochromatographic purification of gibberellins from vegetative tissues of Cucumis sativus L: Separation of 13-hydroxy and 13-desoxygibberellins. Planta 185, 583-586.
61. MacMillan, J. and Beale M.H., (1999) Diterpene Biosynthesis. In Comprehensive Natural Products Chemistry. Vol. 2. (ed. D.E. Cane). Pergamon Press.