Peter Francis Leadlay Date of Birth - Chaires Blaise Pascal

CURRICULUM VITAE
Professor Peter Leadlay, FRS
PERSONAL
Name:
Peter Francis Leadlay
Date of Birth: 13 December 1949
Place of Birth: Sliema, Malta
Nationality: British
Marital Status: Separated, three children
Present position: Professor in Molecular Enzymology, Department of Biochemistry,
University of Cambridge and Chaire Internationale de Recherche
"Blaise Pascal", Institut Pasteur, Paris
EDUCATION AND RESEARCH
1960-66 St Joseph's College, London SE19
1967-71 Govett Open Scholar, New College, Oxford
B. A. Degree Natural Sciences (Chemistry) (First Class Hons.)
1972-74 Senior Scholar, Corpus Christi College, Oxford
D. Phil, 1974 (With Dr J.R. Knowles). M. A. Degree, 1976
1974-76 Royal Society Postdoctoral Fellow, Organic Chemistry
Laboratory, ETH Zürich (with Professor D. Arigoni)
1976-79 Departmental Demonstrator, Department of Biochemistry,
University of Oxford
1976-79 Junior Research Fellow,Wolfson College, Oxford
1977-79 Lecturer in Organic Chemistry, St. Catherine's College, Oxford
1979-84 University Demonstrator, Department of Biochemistry,
University of Cambridge
1979- Fellow, Clare College, Cambridge
1984-95 University Lecturer, Department of Biochemistry,
University of Cambridge
1995-99 University Reader in Molecular Enzymology,
University of Cambridge
1986-98 Director of Studies, Biochemistry and Biology of Cells,
Clare College, Cambridge
1999-2004 Senior (Professorial) Fellow of the Biotechnology and Biological
Sciences Research Council
1999- Professor of Molecular Enzymology, University of Cambridge
2001 – 2003 Chaire Internationale de Recherche "Blaise Pascal", Institut Pasteur
RESEARCH CAREER
Studied mechanistic enzymology with Professor Jeremy Knowles (now at Harvard
University), for the degree of D. Phil. (1974). This work formed an early part of a large and
influential series of papers from the Knowles laboratory on triosephosphate isomerase, the socalled
“perfect enzyme”, and on other enzymes in the glycolytic pathway.
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After Oxford studied as a Royal Society Postdoctoral Research Fellow at the Laboratorium
für organische Chemie, ETH Zürich, 1974-76, with Professor Duilio Arigoni, on the
mechanism of action of coenzyme B 12 -dependent enzymes, gaining expertise in synthetic
organic chemistry, microbiology and natural products chemistry. This period triggered a
long-lasting interest in stereochemical problems in biology, and in the enzymology of natural
products biosynthesis.
First independent (and temporary) research position was as a Departmental Demonstrator in
the Department of Biochemistry, University of Oxford (1976-79), working on the
stereochemical course of various enzyme-catalysed reactions.
Joined the Department of Biochemistry, University of Cambridge in 1979 as an Assistant
Lecturer, was promoted to Lecturer in 1984, Reader in 1995 and Professor in 1999. Since
1979, obtained a succession of project grants from the Medical Research Council, the
Engineering and Physical Sciences/ Biotechnology and Biological Sciences Research
Councils, The Wellcome Trust, European Commission, National Kidney Research Fund, and
Industry, for research into the genetics, enzymology and chemistry of polyketide antibiotic
biosynthesis, and the structure and mechanism of action of coenzyme B 12 -dependent "rearrange-ase"
enzymes. This research (conducted since 1988 jointly with Professor James
Staunton, FRS, of the Department of Chemistry, University of Cambridge) has led to the
identification of the first modular polyketide synthase in 1990, to the first interspecific hybrid
polyketides made by manipulation of polyketide synthase genes in 1994, and to a general
dimeric structural model for modular polyketide synthases in 1996. Over 100 refereed
publications have arisen from this research, and several patents have been applied for. Our
combined group is one of the most active in the world in the area of understanding and
engineering antibiotic polyketide biosynthesis. Also, in 1996 I collaborated with Dr Phil
Evans of MRC, Cambridge in his determination of the first X-ray crystal structure of a B 12 -
“rearrange-ase”, which has revitalized research into this unique class of enzymes.
Together with Professor Staunton, and the University of Cambridge, in late 1996 founded
BIOTICA Technology Limited. The overall aim of BIOTICA is to use for drug discovery the
technology for polyketide biosynthesis discovered and developed in the Cambridge
laboratories. Recently awarded a BBSRC Senior Research Fellowship for scientific
excellence, which guarantees five years (from January 1999) without significant teaching or
administrative commitments. Elected FRS in May 2000.
In June 2002, awarded the Royal Society of Chemistry Celltech Medal for Chemical Biology.
Awarded a visiting part-time professorship (Chaire Internationale de Recherche "Blaise
Pascal") at the Institut Pasteur in Paris from October 2002 to December 2003. This was set up
as a collaboration with the group of Dr Stewart Cole on the modular polyketide synthase that
makes the toxin mycolactone (from Mycobacterium ulcerans), and which is responsible for
the tropical disease Buruli ulcer, for which the only clinical outcomes are either successful
amputation or death.
OTHER APPOINTMENTS
1986-89 Member, British National Committee for Chemistry
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1987-2002 Member, Committee for the Cambridge Centre for Molecular
Recognition (CCMR)
1990 Member, SERC Protein Engineering Review Panel
1991-92 Consultant, Pfizer UK Ltd
1992-93 Consultant, Pfizer Inc., Groton, USA
1992-93 Consultant, BERC, Indian Institute of Technology, Delhi, India.
1992-95 Member, BBSRC-EPSRC Biomolecular Sciences Sub-committee
1996- 2001 Associate Editor, Chemistry & Biology
1996 Co-founder, with Dr J. Staunton and the University of Cambridge, of
BIOTICA Technology Ltd, a company whose aim is the development
of new medicines from engineered natural products.
1996-2001 Director, Technology Foresight Challenge Consortium for Biological
Synthesis of Polyketide Drugs (Funds raised to date: £5 million)
RECENT INVITED SYMPOSIUM LECTURES (1996-2002)
Since 1996 I have delivered a total of 43 invited symposium lectures, 24 outside UK,
including the following:
32 nd Euchem Conference on Stereochemistry, Bürgenstock, May 1997
Gordon Conference on Quinones and Radical Enzymes”, Pisa, May 1997
IUBMB Meeting, San Francisco, August 1998
8 th International Symposium on Genetics of Industrial Microorganisms, Jerusalem, June 1998
Novartis Lecture, Universität Regensburg July 1998
Pfizer Prize Symposium, American Chemical Society Meeting, Boston, August 1998
Gordon Conference on Macromolecular Organization, Oxford, September 1998
Yates Memorial Lecture, University of Toronto, March 1999
Krebs Lecture, University of Sheffield, May 1999
Novartis Chemistry Prize Lecture, Basel, Vienna and Summit, New Jersey, 2001
Royal Pharmaceutical Society, London, 2002
Biotechnology of Microbial Products Conference, Honolulu, Hawaii, 2002
Celltech, Granta Park, Cambridge, 2002
European Bioinformatics Institute, Industry Programme Meeting, Cambridge, December
2002
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PROFESSOR PETER LEADLAY
PUBLICATIONS LIST
(updated 6 th February 2003)
1971
1. Knowles, J.R., Leadlay, P.F. and Maister, S.G. (1971). Triosephosphate isomerase: isotope
studies on the mechanistic pathway. Cold Spring Harbor Symp. Quant. Biol., 36, 157-163.
1976
2. Leadlay, P.F., Albery, W.J. and Knowles, J.R. (1976). Energetics of triosephosphate
isomerase: isotope effects in the enzyme-catalysed reaction. Biochemistry, 15, 5617-5620.
1977
3. Leadlay, P.F., Breathnach, R., Gatehouse, J.A., Johnson, P. and Knowles, J.R. (1977).
Phosphoglycerate mutase from wheat germ: isolation, crystallisation and properties.
Biochemistry, 16, 3050-3053.
1979
4. Leadlay, P.F. (1979). Enzyme Chemistry (a volume in the Chemical Society series of
Monographs for Teachers). The Chemical Society, London.
5. Leadlay, P.F. (1979). (S,S)-diaminopimelate is not an obligatory intermediate in the
biosynthesis of lysine in Corynebacterium glutamicum. FEBS Lett., 98, 399-402.
6. Leadlay, P.F. (1979). Enzyme Chemistry, in Ann. Reports B of the Chemical Society, 472-
485.
1980
7. Armstrong, J., Leadlay, P.F. and Perham, R.N. (1980). Synthesis of methyl [ 3 H]-acetimidate
of high specific radioactivity- a protein-labelling reagent. Anal. Biochem., 109, 410-415
1981
8. Lambiris, S. and Leadlay, P.F. (1981). Modification of enoyl-CoA hydratase with
diethylpyrocarbonate. Biochim. Biophys. Acta, 660, 271-277.
9. Leadlay, P.F. (1981). Purification and properties of methylmalonyl-CoA epimerase from
Propionibacterium shermanii. Biochem. J., 197, 413-419.

1982
10. Leadlay, P.F. and Greer, S. (1982). Synthesis of chiral acetic acids by a simple enzymatic
procedure. Anal. Biochem., 127, 89-92.
1983
11. Fuller, J.Q. and Leadlay, P.F. (1983). Proton transfer in methylmalonyl-CoA epimerase: the
reaction of (2R)-methylmalonyl-CoA in tritiated water. Biochem. J., 213, 643-650.
12. Leadlay, P.F. and Fuller, J.Q. (1983). Proton transfer in methylmalonyl-CoA epimerase:
studies using specifically-tritiated (2R)-methylmalonyl-CoA as substrate. Biochem. J., 213,
635-642.
13. Roberts, G. and Leadlay, P.F. (1983). [ 3 H]-tetrahydrocerulenin, a specific reagent for radiolabelling
fatty acid synthases and related enzymes. FEBS Lett., 159, 13-16.
1984
14. Leadlay, P.F., Roberts, G, and Walker, J.E. (1984). Isolation of a novel calcium-binding
protein from Streptomyces erythreus. FEBS Lett., 178, 157-160.
15. Roberts, G. and Leadlay, P.F. (1984). The use of [ 3 H]-tetrahydrocerulenin to assay
condensing enzyme activity in Streptomyces erythreus. Biochem. Soc. Trans., 11, 642-643.
1985
16. Hale, R.S. and Leadlay, P.F. (1985). The cloning of structural genes for bacterial acyl carrier
proteins. Biochimie, 67, 835-839.
17. Hoving, H., Chrysell, B. and Leadlay, P.F. (1985). Fluorine NMR studies on stereochemical
aspects of the reactions catalysed by transcarboxylase, pyruvate kinase and enzyme I.
Biochemistry, 24, 6163-6169.
1986
18. Francalanci, F., Fuller, J.Q., Davis, N.K., Murfitt, D.M. and Leadlay, P.F. (1986). The
subunit structure of methylmalonyl CoA mutase from Propionibacterium shermanii.
Biochem. J., 236, 489-494.
1987
19. Hale, R.S., Jordan, K. and Leadlay, P.F. (1987). A small, discrete acyl carrier protein is
involved in de novo fatty acid synthesis in Streptomyces erythreus (Saccharopolyspora
erythraea). FEBS Lett., 224, 133-136.
20. Swan, D.G., Hale, R.S., Dhillon, N. and Leadlay, P.F. (1987). A bacterial calcium-binding
protein homologous to calmodulin. Nature, 329, 84-85.

21. Williams, K., Lowe, P.N. and Leadlay, P.F. (1987). Purification and characterization of
pyruvate:ferredoxin oxidoreductase from the anaerobic protozoon Trichomonas vaginalis.
Biochem. J., 246, 529-536.
1988
22. Marsh, E.N., Leadlay, P.F. and Evans, P.R. (1988). Crystallisation and preliminary
diffraction data for adenosylcobalamin-dependent methylmalonyl CoA mutase from
Propionibacterium shermanii. J. Mol. Biol., 200, 421-422.
1989
23. Dhillon, N., Hale, R.S., Cortés, J. and Leadlay, P.F. (1989). Cloning, nucleotide sequence,
and the effects of disruption of a gene from Saccharopolyspora erythraea (Streptomyces
erythraeus) which is involved in erythromycin biosynthesis. Molec. Microbiol., 3, 1405-1414.
24. Marsh, E.N. and Leadlay, P.F. (1989). Methylmalonyl CoA mutase from Propionibacterium
shermanii: evidence for the presence of two masked thiols. Biochem. J., 260, 339-343.
25. Marsh, E.N., McKie, N., Davis, N.K. and Leadlay, P.F. (1989). Cloning and structural
characterisation of the genes encoding adenosylcobalamin-dependent methylmalonyl CoA
mutase from Propionibacterium shermanii. Biochem. J., 260, 345-352.
26. Marsh, E.N., Harding, S.E. and Leadlay, P.F. (1989). Subunit interactions in methylmalonyl
CoA mutase studied by analytical ultracentrifugation. Biochem. J., 260, 353-358.
27. Swan, D.G., Hale, R.S., Cortés,J. and Leadlay, P.F. (1989). Expression of an EF hand
calcium-binding protein from Saccharopolyspora erythraea in Streptomyces lividans and
Escherichia coli. J. Bacteriol., 171, 5614-5619.
1990
28. Caffrey, P., Green, B., Packman, L.C., Rawlings, B.J., Staunton, J. and Leadlay, P.F. (1990).
An acyl carrier protein-thioesterase domain of the 6-deoxyerythronolide B synthase of
Saccharopolyspora erythraea: expression in Escherichia coli, purification and
characterisation. Eur. J. Biochem., 195, 823-830.
29. Cortés, J., Haydock, S.F., Roberts, G.A., Bevitt, D.J. and Leadlay, P.F. (1990). An unusually
large multifunctional polypeptide in the erythromycin-producing polyketide synthase of
Saccharopolyspora erythraea. Nature, 348, 176-178.
30. Dhillon, N. and Leadlay, P.F. (1990). A repeated decapeptide motif in the C-terminal domain
of the ribosomal RNA methylase of the erythromycin producer Saccharopolyspora erythraea.
FEBS Lett., 262, 189-193.
31. Leadlay, P.F. (1990). Structural studies on adenosylcobalamin-dependent methylmalonyl
CoA mutase. In Cobalamin 88 (Bhatt, R. and Linnell, J.C., eds.), 321-328.

32. Leadlay, P.F. and Ledley, F.D. (1990). Sequence homologies between the structural genes for
human and bacterial methylmalonyl CoA mutases. In Cobalamin 88 (Bhatt, R. and Linnell,
J.C., eds.), 341-352.
33. McKie, N., Patchett, M.L., Keep. N.H. and Leadlay, P.F. (1990). Adenosylcobalamindependent
methylmalonyl CoA mutase from Propionibacterium shermanii: active
holoenzyme produced from Escherichia coli. Biochem. J., 269, 293-298.
34. Williams, K.P., Leadlay, P.F. and Lowe, P.N. (1990). Inhibition of pyruvate:ferredoxin
oxidoreductase from Trichomonas vaginalis by pyruvate and its analogues; comparison with
the pyruvate decarboxylase component of the pyruvate dehydrogenase complex. Biochem. J.,
268, 69-75.
1991
35. Bridges, A.M., Leadlay, P.F., Revill, W.P. and Staunton, J. (1991). Use of electrospray mass
spectrometry to assay chemical reactivity of an acyl carrier protein involved in fatty acid
biosynthesis in Saccharopolyspora erythraea., J. Chem. Soc., Chem. Commun., 11, 776.
36. Bridges, A.M., Leadlay, P.F., Revill, W.P. and Staunton. J. (1991). Use of electrospray mass
spectrometry in enzymic studies on the acyl carrier protein implicated in fatty acid
biosynthesis in Saccharopolyspora erythraea. J. Chem. Soc., Chem. Commun., 11, 778.
37. Revill, W.P. and Leadlay, P.F. (1991). Cloning, characterization and high-level expression in
Escherichia coli of the Saccharopolyspora erythraea gene encoding an acyl carrier protein
potentially involved in fatty acid biosynthesis. J. Bacteriol., 173, 4379-4385.
38. Revill, P., Hale, R.S., Cortés, J. and Leadlay, P.F. (1991). The cloning, nucleotide sequence,
and expression in Escherichia coli of an acyl carrier protein gene from the fatty acid synthase
gene cluster of Saccharopolyspora erythraea (Streptomyces erythraeus). J. Bacteriol., 173,
4379-4385.
1992
39. Caffrey, P., Bevitt, D., Staunton, J. and Leadlay, P.F. (1992). Identification of DEBS 1,
DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin-producing
polyketide synthase from Saccharopolyspora erythraea. Federation of European
Biochemical Societies, 304, 225.
1993
40. Leadlay, P.F., Staunton, J., Aparicio, J.F., Bevitt, D.J., Caffrey, P., Cortés, J., Marsden, A.
and Roberts, G.A. (1993). The erythromycin-producing polyketide synthase. Biochemical
Society Transactions, 21, 218.
41. Morris, S.A., Revill, W.P., Staunton, J. and Leadlay, P.F. (1993). Purification and separation
of holo-forms and apro-forms of Saccharopolyspora erythraea acyl-carrier protein released
from recombinant Escherichia coli by freezing and thawing. Biochem. J., 294, 521.

42. Roberts, G.A., Staunton, J. and Leadlay, P.F. (1993). Heterologous expression in Escherichia
coli of an intact multienzyme component of the erythromycin-producing polyketide synthase.
European Journal of Biochemistry, 214, 305.
1994
43. Aparicio, J.F., Caffrey, P., Marsden, A.F.A., Staunton, J. and Leadlay, P.F. (1994). Limited
proteolysis and active-site studies of the first multienzyme component of the erythromycinproducing
polyketide synthase. Journal of Biological Chemistry, 269, 8524.
44. Dutton, C.J., Hooper, A.M., Leadlay, P.F. and Staunton, J. (1994). Avermectin biosynthesis -
intact incorporation of a diketide chain-assembly intermediate into the polyketide
macrocyclic ring. Tetrahedron Lett., 35, 327.
45. Hailes, H.C., Handa, S., Leadlay, P.F., Lennon, I.C., Ley, S.V. and Staunton, J. (1994).
Biosynthesis of tetronasin. Part 2. Identification of the tetraketide intermediate attached to the
polyketide synthase. Tetrahedron Lett., 35, 311.
46. Hailes, H.C., Handa, S., Leadlay, P.F., Lennon, I.C., Ley, S.V. and Staunton, J. (1994).
Biosynthesis of tetronasin. Part 3. Preparation of deuterium-labelled triketides and
tetraketides as putative biosynthetic precursors of tetronasin. Tetrahedron Lett., 35, 315.
47. Hailes, H.C., Jackson, C.M., Leadlay, P.F., Ley, S.V. and Staunton, J. (1994). Biosynthesis of
tetronasin. Part 1. Introduction and investigation of the diketide and triketide intermediates
bound to the polyketide synthase. Tetrahedron Lett., 35, 307.
48. Marsden, A.F.A., Caffrey, P., Aparicio, J.F., Loughran, M.S., Staunton, J. and Leadlay, P.F.
(1994). Stereospecific acyl transfers on the erythromycin-producing polyketide synthase.
Science, 263, 378.
1995
49. Aggarwal, R., Caffrey, P., Leadlay, P.F., Smith, C.J. and Staunton, J. (1995). The thioesterase
of the erythromycin-producing polyketide synthase: mechanistic studies in vitro to investigate
its mode of action and substrate specificity. J. Chem. Soc., Chem. Commun., 15, 1519-1520.
50. Brown, M.J.B., Cortés, J., Cutter, A.L., Leadlay, P.F. and Staunton, J. (1995). A mutant
generated by expression of an engineered DEBS1 protein from the erythromycin-producing
polyketide synthase (PKS) in Streptomyces coelicolor produces the triketide as a lactone, but
the major product is the nor-analogue derived from acetate as starter acid. J. Chem. Soc.,
Chem. Commun., 15, 1517-1518.
51. Cortés, J., Wiesmann, K.E.H., Roberts, G.A., Brown, M.J.B., Staunton, J. and Leadlay, P.F.
(1995). Repositioning of a domain in a modular polyketide synthase to promote specific chain
cleavage. Science, 268, 1487-1489.

52. Haydock. S.F., Aparicio, J. F., Molnár, I., Schwecke, T., Khaw, L.E., König, A., Marsden,
A.F.A., Galloway, I.S., Staunton, J. and Leadlay, P.F. (1995). Divergent sequence motifs
correlated with the substrate specificity of (methyl)malonyl-CoA: ACP transacylase domains
in modular polyketide synthases. FEBS Lett., 374, 246-248.
53. Schwecke, T., Aparicio, J.F., Molnár, I., König, A., Khaw, L.E., Haydock, S.F., Oliynyk, M.,
Caffrey, P., Cortés, J., Lester, J.B., Böhm, G.A. Staunton, J. and Leadlay, P.F. (1995). The
biosynthetic gene-cluster for the polyketide immunosuppressant rapamycin. Proceedings of
the National Academy of Sciences of the United States of America, 92, 7839-7843.
54. Wiesmann, K.E.H., Cortés, J., Brown, M.J.B., Cutter, A.L., Staunton, J. and Leadlay, P.F.
(1995). Polyketide synthesis in vitro on a modular polyketide synthase. Chemistry & Biology,
2, 583-589.
1996
55. Aparicio, J.F., Molnár, I., Schwecke, T., König, A., Haydock, S.F., Khaw, L. E., Staunton, J.
and Leadlay, P.F. (1996). Organization of the biosynthetic gene cluster for rapamycin in
Streptomyces hygroscopicus - analysis of the enzymatic domains in the polyketide synthase.
Gene, 169, 9-16.
56. König, A., Schwecke, T., Molnár, I, Böhm, G.A., Lowden, P.A.S., Staunton, J. and Leadlay,
P.F. (1996). The nature of the starter unit for the rapamycin polyketide synthase. Angew.
Chemie. Intl. Edn. Engl., 35, 2249-2251.
57. Less, S.L., Handa, S. Leadlay, P.F., Dutton, C.J. and Staunton, J. (1996). Biosynthesis of
tetronasin 5. Novel fluorinated and non-fluorinated analogues of tetronasin via intact
incorporation of diketide, triketide and tetraketide analogue precursors. Tetrahedron Lett., 37,
3511-3514.
58. Less, S.L., Handa, S., Millburn, K., Leadlay, P.F., Dutton, C.J. and Staunton, J. (1996).
Biosynthesis of tetronasin 6. Preparation of structural analogues of the diketide and triketide
biosynthetic precursors to tetronasin. Tetrahedron Lett., 37, 3515-3518.
59. Less, S.L., Leadlay, P.F., Dutton, C.J. and Staunton, J. (1996). Biosynthesis of tetronasin 7.
Preparation of structural analogues of the tetraketide biosynthetic precursor to tetronasin.
Tetrehedron Lett., 37, 3519-3520.
60. Lowden, P.A.S., Böhm, G.A., Staunton, J. and Leadlay, P.F. (1996). The nature of the starter
unit for the rapamycin polyketide synthase. Angewandte Chemie lntl. Edn. Engl., 35, 2249-
2251.
61. Mancia. F., Keep, N.H., Nakagawa, A., Leadlay, P.F., McSweeney, S., Rasmussen, B.,
Bösecke, P., Diät, O. and Evans, P. R. (1996). How coenzyme B 12 radicals are generated - the
crystal structure of methylmalonyl-CoA mutase at 2 angstroms resolution. Structure, 4, 339-
350.
62. Meier, T., Thomä, N. and Leadlay, P.F. (1996). Tritium isotope effects in adenosylcobalamindependent
methylmalonyl-CoA mutase. Biochemistry, 35, 11791-11796.

63. Molnár, I., Aparicio, J.F., Haydock, S.F., Khaw, L.E., Schwecke, T., König, A., Staunton, J.
and Leadlay, P.F. (1996). Organization of the biosynthetic gene cluster for rapamycin in
Streptomyces hygroscopicus - analysis of genes flanking the polyketide synthase. Gene, 169, 1-
7.
64. Oliynyk, M., Brown, M.J.B., Cortés, J., Staunton, J. and Leadlay, P.F. (1996). A hybrid
modular polyketide synthase obtained by domain swapping. Chemistry & Biology, 3, 833-839.
65. Staunton, J., Caffrey, P., Aparicio, J.F., Roberts, G.A., Bethell, S.S. and Leadlay, P.F. (1996).
Evidence for a double-helical structure for modular polyketide synthases. Nature Structural
Biology, 3, 188-192.
66. Thomä, N. and Leadlay, P.F. (1996). Homology modeling of human methylmalonyl-CoA
mutase - a structural basis for point mutations causing methylmalonic aciduria. Protein Sci., 5,
1922-1927.
1997
67. Gaisser, S., Böhm, G.A., Cortés, J. and Leadlay, P.F. (1997). Analysis of seven genes from
the eryAl/eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora
erythraea. Molecular & General Genetics, 256, 239-251.
68. Galloway, I.S., Rowe, C.J., Cortés, J., Staunton, J. and Leadlay, P.F. (1997). A system for the
enhanced expression of genes in Saccharopolyspora erythraea and its use in the production
of novel polyketides. Faseb Journal, 11, 1680.
69. König, A., Schwecke, T., Molnár, I., Böhm, G.A., Lowden, P.A.S., Staunton, J. and Leadlay,
P.F. (1997). The pipecolate-incorporating enzyme for the biosynthesis of the
immunosuppressant rapamycin - nucleotide sequence analysis, disruption and heterologous
expression of rapP from Streptomyces hygroscopicus. European Journal of Biochemistry,
247, 526- 534.
70. Leadlay, P.F. (1997). Combinatorial approaches to polyketide biosynthesis. Current opinion
in Chemical Biology, 1, 162-168.
71. Leadlay, P.F. (1997). Structure and mechanism of modular polyketide synthases. Faseb
Journal, 11, 2548.
72. Lewis, H.D., Floriano, B., Linton, K.J., White, J., Bibb, M.J., Hunter, I.S. and Leadlay, P.F.
(1997). Evidence for a novel mechanism of resistance to the polyether polyketide tetronasin.
Faseb Journal, 11, 1022.
73. Oliynyk, M., Brown, M.J.B. and Leadlay, P.F. (1997). Engineering of polyketide biosynthesis
by domain replacements in a modular polyketide synthase. Faseb Journal, 11, 2644.

74. Staunton, J., Leadlay, P.F., Marsden, A.F.A., Wilkinson, B., Dunster, N.J., Cortés, J.,
Oliynyk, M., Hanefeld U. and Brown M.J.B., (1997). Rational engineering of polyketide
biosynthesis: Where do we begin Developments in Industrial Microbiology - GMBIM,
edited by Baltz, R.H., Hegeman, G.D., and Skatrud, P.L., American Society for
Microbiology, Washington DC.
75. Weissman, K.J., Timoney, M., Bycroft, M., Grice, P., Hanefeld, U., Staunton, J. and Leadlay,
P.F. (1997). The molecular basis of Celmer's rules: The stereochemistry of the condensation
step in chain extension on the erythromycin polyketide synthase. Biochemistry, 36, 13849-
13855.
1998
76. Böhm, I., Holzbaur, I.E., Hanefeld, U., Cortés, J., Staunton, J. and Leadlay, P.F. (1998).
Engineering of a minimal modular polyketide synthase, and targeted alteration of the
stereospecificity of polyketide chain extension. Chemistry & Biology, 5, 407-412.
77. Cutter, A.L., Hanefeld, U., Wilkinson, B., Leadlay, P.F. and Staunton, J. (1998).
Enantiospecific synthesis of tetrasubstituted δ-lactones. Tetrahedron Lett., 39, 9827-9830.
78. Gaisser, S., Böhm, G.A., Doumith, M., Raynal, M.C., Dhillon, N., Cortés, J. and Leadlay,
P.F. (1998). Analysis of eryBI eryBIII and eryBVII from the erythromycin biosynthetic gene
cluster in Saccharopolyspora erythraea. Molecular & General Genetics, 258, 78-88.
79. Gaisser, S. and Leadlay, P.F. (1998). Sugaring the pill by design. Nature Biotechnology, 16,
19-20.
80. Khaw, L.E., Böhm, G.A., Metcalfe, S., Staunton, J. and Leadlay, P.F. (1998). Mutational
biosynthesis of novel rapamycins by a strain of Streptomyces hygroscopicus NRRL 5491
disrupted in rapL, encoding a putative lysine cyclodeaminase. Journal of Bacteriology, 180,
809-814.
81. Marsden, A.F.A., Wilkinson, B., Cortés, J., Dunster, N.J., Staunton, J. and Leadlay, P.F.
(1998). Engineering broader specificity into an antibiotic-producing polyketide synthase.
Science, 279, 199-202.
82. Pacey, M.S., Dirlam, J.P., Geldart, R.W., Leadlay, P.F., McArthur, H.A.I., McCormick, E.L.,
Monday, R.A., O'Connell, T.N., Staunton, J. and Winchester, T.J. (1998). Novel
erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL 2338 pIG1. I.
Fermentation, isolation and biological activity. J. Antibiotics, 51, 1029-1034.
83. Rowe, C.J., Cortés, J., Gaisser, S., Staunton, J. and Leadlay, P.F. (1998). Construction of new
vectors for regulated high-level expression in actinomycetes. Gene, 216, 215-223.
84. SalahBey, K., Doumith, M., Michel, J.M., Haydock, S., Cortés, J., Leadlay, P.F. and Raynal,
M.C. (1998). Targeted gene inactivation for the elucidation of deoxysugar biosynthesis in the
erythromycin producer Saccharopolyspora erythraea. Molecular & General Genetics, 257,
542-553.

85. Thomä, N.H. and Leadlay, P.F. (1998). Mechanistic and structural studies on methylmalonyl-
CoA mutase. Biochemical Soc. Trans., 26, 293-298.
86. Thomä, N.H., Meier, T.W., Evans, P.R. and Leadlay, P.F. (1998). Stabilization of radical
intermediates by an active site tyrosine residue in methylmalonyl-CoA mutase. Biochemistry
37, 14386-14393.
87. Weissman, K.J., Smith, C.J., Hanefeld, U., Aggarwal, R., Bycroft, M., Staunton, J. and
Leadlay, P.F. (1998). The thioesterase of the erythromycin-producing polyketide synthase:
Influence of acyl chain structure on the mode of release of substrate analogues from the acyl
enzyme intermediates. Angewandte Chemie-International Edition, 37, 1437-1440.
88. Weissman, K.J., Bycroft, M., Cutter, A.L., Hanefeld, U., Frost, E.J., Timoney, M.C., Harris,
R., Handa, S., Roddis, M., Staunton J. and Leadlay, P.F. (1998). Evaluating the efficiency of
precursor-directed biosynthesis towards novel erythromycins through in vitro studies on a
bimodular polyketide synthase. Chemistry & Biology, 5, 743-754.
89. Weissman, K.J., Bycroft, M., Staunton, J. and Leadlay, P.F. (1998). Origin of starter units for
erythromycin biosynthesis. Biochemistry, 37, 11012-11017.
1999
90. Bisang, C., Long, P.F., Cortés, J., Westcott, J., Crosby, J., Matharu, A-L., Cox, R.J., Simpson,
T.J., Staunton, J. and Leadlay, P.F. (1999). A chain initiation factor common to both modular
and aromatic polyketide synthases. Nature, 40, 502-505.
91. Gaisser, S., Reather, J., Wirtz, G., Kellenberger, L., Staunton, J. and Leadlay, P.F. (1999) A
defined system for hybrid macrolide biosynthesis in Saccharopolyspora erythraea.
Molecular Microbiology, 36, 391-401.
92. Gates, P.J., Kearney, G.C., Jones, R., Leadlay, P.F. and Staunton, J. (1999). Structural
elucidation studies of erythromycins by electrospray tandem mass spectrometry. Rapid
Commun. in Mass Spectrom., 13, 242-246.
93. Holzbaur, I.E., Harris, R.C., Bycroft, M., Cortés, J., Bisang, C., Staunton, C., Rudd, B.A.M.
and Leadlay, P.F. (1999). Molecular basis of Celmer's rules: the role of two ketoreductase
domains in the control of chirality by the erythromycin modular polyketide synthase.
Chemistry & Biology, 6, 189-195.
94. Kearney, G.C., Gates, P.J., Leadlay, P.F., Staunton, J. and Jones, R. (1999). Structural
elucidation studies of erythromycins by electrospray tandem mass spectrometry II. Rapid
Commun. in Mass Spectrom., 13, 1650-1656.
95. Large, K.P., Mirjalili, N., Osborne, M., Peacock, L.M., Zormpaidis, V., Walsh, M.,
Cavanagh, M.E., Leadlay, P.F. and Ison, A.P. (1999). Lipase activity in Streptomycetes.
Enzyme and Microbial Technology, 25, 569-575.

96. Mirjalili, N., Zormpaidis, V., Leadlay, P.F. and Ison, A.P. (1999) The effect of rapeseed oil
uptake on the production of erythromycin and triketide lactone by Saccharopolyspora
erythraea. Biotechnology Progress, 15, 911-918
97. Ranganathan, A., Timoney, M., Bycroft, B., Cortés, J., Thomas, I.P., Wilkinson, B.,
Kellenberger, L., Hanefeld, U., Galloway, I.S., Staunton, J. and Leadlay, P.F. (1999).
Knowledge-based design of bimodular and trimodilar polyketide synthases based on domain
and module swaps: a route to simple statin analogues. Chemistry & Biology, 6, 731-741.
98. Weissman, K.J., Kearney, G.C., Leadlay, P.F. and Staunton, J. (1999). Structural elucidation
studies of polyketide tetrasubstituted δ-lactones by gas chromatography/tandem mass
spectrometry and electrospray mass spectrometry. Rapid commun. in Mass Spectrom., 13,
2103-2108.
2000
99. Bycroft, M., Weissman, K.J, Staunton J. and Leadlay, P.F. (2000) Efficient purification and
kinetic characterisation of a bimodular derivative of the erythromycin polyketide synthase.
Eur. J. Biochem., 267, 520-526.
100. Gaisser, S., Reather, J., Wirtz, G., Kellenberger, L., Staunton, J. & Leadlay, P.F. (2000) A
defined system for hybrid macrolide biosynthesis in Saccharopolyspora erythraea.
Molecular Microbiology, 36, 391-401.
101. Thomä, N.H., Evans, P.R. and Leadlay, P.F. (2000). Protection of radical intermediates at
the active site of adenosylcobalamin-dependent methylmalonyl-CoA mutase. Biochemistry
39, 9213-9221.
102. Wilkinson, B., Foster, G., Rudd, B.A.M., Taylor, N.L., Blackaby, A.P., Sidebottom, P.J.,
Cooper, D.J., Dawson, M.J., Buss, A.D., Gaisser, S., Böhm, I.U., Rowe, C.J., Cortés, J.,
Leadlay, P.F. and Staunton, J. (2000) Novel octaketide macrolides related to 6-
deoxyerythronolide B provide evidence for iterative operation of the erythromycin
polyketide synthase. Chemistry & Biology, 7, 111-117.
2001
103. Gaisser, S., Lill, R., Wirtz, G., Grolle, F., Staunton, J., and Leadlay, P.F. (2001) New
erythromycin derivatives from Saccharopolyspora erythraea using sugar O-
methyltransferases from the spinosyn biosynthetic gene cluster. Molec. Microbiol. 41,
1223-1231.
104. Heathcote, M. L., Staunton, J., and Leadlay, P. F. (2001) Role of Type II thioesterases:
evidence for removal of short acyl chains produced by aberrant decarboxylation of chain
extender units/ Chemistry & Biology 8, 207-220.
105. Holzbauer, I. E., Ranganathan, A., Thomas, I.P., Kearney, D.J.A., Reather, J.A., Rudd,
B.A.M., Staunton, J., and Leadlay, P.F. (2001) Molecular basis of Celmer’s rules: role of
the ketosynthase domain in epimerisation and demonstration that ketorductase domains can
have altere product specificity with unnatural substrates. Chemistry & Biology 8, 329-340.

106. Rowe, C.J., Böhm, I.U., Thomas, I.P., Wilkinson, B., Rudd, B.A.M., Foster, G., Blackaby,
A.P., Sidebottom, P.J., Roddis, Y., Buss, A.D., Staunton, J., and Leadlay, P.F. (2001)
Engineering a polyketide with a longer chain by insertion of an extra module into the
erythromycin-producing polyketide synthase. Chemistry & Biology 8, 475-485.
107. Weissman, K. J., Kearney, G.C., Timoney, M.C. Bycroft, M., Grice, P., Hanefeld, U.,
Staunton, J., and Leadlay, P.F. (2001) Use of isotopes to investigate the mechanism of
stereocontrol in the biosynthesis of erythromycin. In : Synthesis and applications of
isotopically labelled compounds, Volume 7 (Eds Pleiss, U. & Voges, R.). John Wiley and
Son, New York, pp. 631-635.
2002
108. Gaisser, S., Lill, R., Staunton, J., Mendez, C., Salas, J., and Leadlay, P.F. (2002) Parallel
pathways for oxidation of 14-membered polyketide macrolactones in Saccharopolyspora
erythraea Molec. Microbiol. 44, 771-781.
109. Leadlay, P. F., Staunton, J., Oliynyk, M, Bisang, C., Cortés, J., Frost, E., Hughes-Thomas,
Z.A., Jones, M.A., Kendrew, S.G., Long, P.F., McArthur, H.A.I., McCormick, E.L.,
Oliynyk, Z., Stark, C.B.W., and Wilkinson, C.J. (2002) Engineering of complex polyketide
biosynthesis – insights from sequencing of the monensin biosynthetic gene cluster. J.
Industrial Molec Microbiol. 27,360-367.
110. Long, P. F., McCormick, E., Cortes, J., Wilkinson, C. J., Bisang, C.P., McArthur, H.,
Staunton, J., and Leadlay, P.F. (2002) Engineering specificity of starter unit selection by
the erythromycin-producing polyketide synthase. Molec. Microbiol 43, 1215-1225.
111. Thomas, I., Martin, C.J., Wilkinson, C.J., Staunton, J., and Leadlay, P.F (2002) Skipping in
a hybrid polyketide synthase: evidence for ACP to ACP chain transfer. Chemistry &
Biology, 9, 781-787.
112. Østergaard, L. H., Kellenberger, L., Cortes, J., Roddis, M.P., Deacon, M., Staunton, J., and
Leadlay, P.F. (2002) Stereochemistry of catalysis by the ketoreductase activity in the first
extension module of the erythromycin polyketide synthase. Biochemistry, 41, 2719-2726.
113. Wilkinson,,C. J., Frost, E. J., Staunton, J. and Leadlay, P. F. (2002) Chain initiation on the
soraphen-producing modular polyketide synthase from Sorangium cellulosum. Chemistry &
Biology, 8, 1197-1208.
114. Wilkinson , C.J., Hughes Thomas, Z.A., Rowe, C.J. Bohm, I., Mironenko, T., Deacon, M.
Wheatcroft, M., Wirtz, G., Staunton, J., and Leadlay, P.F. (2002) Increasing the efficiency
of heterologous promoters in actinomycetes. Journal of Molecular Microbiology &
Biotechnology, 4, 417-26.

In Press
Oliynyk, M., Stark, C.B.W., Bhatt, A., Jones, M.A., Hughes-Thomas, Z.A., Oliynyk, Z.,
Demydchuk, Y., Staunton, J. and Leadlay, P.F. (2003) Analysis of the biosynthetic gene cluster
for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of
monB and monC genes in oxidative cyclistion. Journal of Molecular Microbiology.
Submitted
Gaisser, S., Kellenberger, L., Kaja, A.L., Weston, A.J., Lill, R.E., Wirtz, G., Kendrew, S.G.,
Low, L., Wilkinson, B., Galloway, I.S., Stutzman-Engwall, K., McArthur, H.A.I., Staunton, J.
and Leadlay, P.F. Direct production of ivermectin-like drugs after domain exchange in the
avermectin polyketide synthase of Streptomyces avermitilis ATCC31272.