Principal Supervisor name,
Prof G. L. Challis, Department of Chemistry,
University of Warwick
Second Supervisor name,
Dr Lijiang Song, Department of Chemistry,
University of Warwick
Chemical Biology Research Laboratory, Department of Chemistry,
University of Warwick
PhD project title:
Elucidating and exploiting
natural product biosynthesis
atural products have myriad applications,
including: pharmaceuticals, flavours and fragrances, crop
chemical synthesis. Microorganisms have an extraordinary capacity to produce
natural products with a wide ra
nge of bioactivities. These
essive, insecticidal, herbicidal and fungicidal
The biosynthetic pathways for microbial natural products typically involve dozens of enzymes and are
subject to tight temporal regulation. Thus
remarkable and highly complex
biological systems. Elucidating the molecular mechanisms of
and exploiting the
knowledge gained for bioengineering of the biosynthetic pathways
to boost titres or produce novel
natural product analogues (often r
eferred to as “metabolic engineering”)
is a cornerstone of the
rapidly emerging field of industrial biotechnology.
This project will exploit a highly interdisciplinary approach to elucidating and exploiting bioactive
natural product biosynthesis i
n bacteria belonging to the
(and related actinobacteria)
genera. A student working on the project will develop skills in most, if not all, of the
natural product isolation and structure elucidation;
manipulation; protein overproduction, purification and characterisation; enzymology;
and a wide variety of spectroscopic methods.
We are currently investigating the biosynthetic pathways to a dive
rse array of bioactive metabolites
from such bacteria
, including enacyloxin IIa (antibacterial), the bottromycins (antibacterial),
methylenomycin A (antibacterial), coelimycins (antibacterial), the stambomycins (anticancer),
streptorubin B (antimalaria
l), quartromicin A (antiviral), thaxtomin A (herbicidal), desferrioxamines
The precise focus of the project will be determined by mutual agreement between
the student and the supervisors.
microbiology; natural product isolation and structure elucidation;
molecular genetic manipulation; protein overproduction, purification and characterisation;
ray crystallography; organic synthesis; and a wide variety of spectroscopic methods
S.W. Haynes, P.K. Sydor, C. Corre, L. Song and G.L. Challis. Stereochemical elucidation of
J. Am. Chem. Soc.
R. Bunet, L. Song, M.V. Mendes, C. Corre, L. Hotel, N. Rouhier, X. Framboisier, P. Leblond,
Challis and B. Aigle
Characterization and manipulation of the pathway
specific late regulator
as a new producer of kinamycins.
L. Laureti, L. Song, S. Huang, C. Corre, P. Leblo
nd, G.L. Challis and B. Aigle. Identification of a
membered macrolide complex by activation of a silent polyketide synthase in
Proc. Natl. Acad. Sci. USA
P.K. Sydor, S. M. Barry, O.M. Odulate
, F. Barona
Gomez, S.W. Haynes, C. Corre, L. Song, and G.L.
Regio and stereodivergent antibiotic oxidative carbocyclizations catalyzed by Rieske
C. Davis, S. Carberry, M. Schrettl, I. Singh, J.C
. Stephens, S.M. Barry, K. Kavanagh,
G.L. Challis, D.
Brougham, and S. Doyle. The role of glutathione S
transferase GliG in gliotoxin biosynthesis in
E. Mahenthiralingam, L. Song, A. Sass, J. White, C.
Wilmot, A. Marchbank, O. Boaisha, J. Paine, D.
Knight and G. L. Challis. Enacyloxins are the products of an unusual hybrid polyketide synthase
encoded by a cryptic
AMMD gene cluster.
J.R. Whicher, G.
Sydor, R. Singh , M. Alhamadsheh, G.L. Challis, K.A. Reynolds and
Structure and Function of RedJ, a thioesterase from the prodiginine biosynthetic
J. Biol. Chem.
Papireddy, M. Smilkstein, J. X. Kelly, Shweta, S. M. Salem, M. Alhamadsheh, S. W. Haynes, G. L
Challis, and K.A. Reynolds. Antimalarial Activity of Natural and Synthetic Prodiginines.
R.F. Seipke, L. Song, J. Bicz, P. Las
karis, A. Yaxley, G.L. Challis and R. Loria.
The plant pathogen
22 has a functional pyochelin biosynthetic pathway that is regulated by
S. Schmelz, C.H. Botting,
L. Song, N. Kadi, G.L. Challis and J.H. Naismith. Structural basis for acyl
acceptor specificity in the achrombactin biosynthetic enzyme AcsD.
J. Mol. Biol.
S. Lautru, L. Song, L. Demange, T. Lombes, H. Galons, G.L. Challis and J.
rnodet. A sweet
the key congocidine precursor 4
Angew. Chem. Int.
Gomez, L. Song, D. J. Fox, M. J. Bibb and G. L. Challis.
Structure and biosynthesis
of the unusual polyke
tide alkaloid coelimycin P1, a metabolic product of the
gene cluster of
S.M. Barry, E.R. Johnson, J.A. Kers, L. Song, P.R. Aston, B. Patel, S.B. Krasnoff
, B.R. Crane, D.M.
Gibson, R. Loria and G. L. Challis.
tryptophan nitration in
thaxtomin phytotoxin biosynthesis
Nat. Chem. Biol.
Gomez, L. Song, M.J. Bibb and G.L. Challis. Posttranslational
macrolactamidination in the assembly of the bottromycin complex of ribosomal peptide
Please state below which hazards may be connected with this studentship:
The studentship will entail work
high toxicity and category 1 or 2 substances
phosphate or carbamate pesticides
Skin or respiratory sensitising agents (e.g. insect parts, organic
dusts from animals, spores, pollen, antibiotics, fibres, chemical
sensitisers, wood dust etc)
Significant manual handling
Mechanical repetition where the frequency and
Working in areas where there are temperature extremes
Driving vehicles (tractors, fork lifts, ATVs etc)
Crop planting, harvesting, recording or grading
Working in close proximity to bees or other stinging insects
Working at height [>2 m] (using various types of access
Working with noisy or vibrating equipment
Working at night (between 11.00pm and 6.00am)
Other significant hazards (specify)