PhD in Chemical Biology
Studies on the biosynthesis of non-ribosomal peptides
University of Cambridge, UK
Masters in Chemistry
University of Oxford, UK
2023 - date
UK Young Academy | Royal Society
2019 - date
Lecturer of Biomedical Science
University of York
2018 - 2021
Turing Fellow
Alan Turing Institute London
2015 - 2020
Fellow of Natural Sciences
Downing College, University of Cambridge
2015 - 2020
Senior Research Associate
Cancer Research UK Cambridge Research Institute
2013 - 2014
Research Associate
Cancer Research UK Cambridge Research Institute
2009 - 2013
Career Development Fellow
MRC Laboratory of Molecular Biology
2005 - 2009
PhD student
Deparment of Chemistry, University of Cambridge, UK
Advisors: Dr. J. Spencer and Dr. F. Leeper
2024 EPSRC Summer Studentship
2024 Great Ormond Street Hospital Charity - National Grant
2024 Industrial Partnership Fund
2023 MRC Research Grant (Co-I)
2023 BBSRC Japan partnering award
2023 BBSRC Australia partnering award
2022 ROMitigation Fund (International Partnerships), BBSRC
2022 BBSRC 21ALERT mid-range equipment initiative
2021 Research Grant, Royal Society (Co-I)
2021 University Priming Fund, University of York
2021 BBSRC Responsive Mode Grant, UKRI
2021 Biochemical Society Scientific Outreach Grants
2020 Funded Visiting Fellow, Pomona College, California (Cancelled due to Covid)
2020 Turing Project Grant, Alan Turing Institute
2019 Wellcome, Centre for Future Health, Career Establishment Award
2019 Funded Visiting Lecturer, Keio University, Toyko
2018 Turing Fellowship, Alan Turing Institute
2017 Thomas Jefferson Visiting Fellow, University of Virginia
2017 CRUK Research Travel Award
2015 CRUK Rising Star in Research Engagement Prize
2015 Fellow, Downing College, University of Cambridge
2014 Unltd Try-It Award
2013 College Lecturer and Bye-Fellow Downing College
2012 Wellcome Trust People Award
2012 British Mass Spectrometry Society Travel Award
2012 MRC Award via the Special Awards Scheme for contributions to the MRC
2012 British Science Association Media Fellowship
2011 UnLtd Catalyst Award for Social Entrepreneurship
2009 MRC Career Development Fellowship
2005 BBSRC PhD Studentship
2020 Member Royal Society of Biology
2015 Fellow of the Higher Education Academy
2014 Member Biochemical Society
1These authors contributed equally to this work.
* Corresponding author.
Abstract: The problem of bacterial resistance is of growing concern within the medical community. Eventually, even with responsible use of antibiotics, new compounds will be required to bypass the resistance that bacteria have acquired. Thus the expansion of knowledge and understanding of antibiotics is key in the development of new compounds in the fight against infection. One attractive starting point for the development of new compounds are those natural products generated by non-ribosomal peptide synthetases (NRPS), which include a range of clinically relevant glycopeptide antibiotics.
Several aspects of the biosynthesis of glycopeptide antibiotics were examined: first, the investigation to identify, by the use of directed evolution if 4-hydroxymandelic acid synthase (HmaS) from the gene cluster of the antibiotic chloroeremomycin may have evolved from its homologue 4-hydroxyphenylpyruvate dioxygenase (HppD). The summation of this work is published in FEBS Lett. 2006; 580:3445. Following on from this work was an investigation into the hypothesis that HmaS catalyses the turnover of the non-natural phenylpyruvic acid to produce a product with an inverted chiral centre compared to that of the natural substrate due to differences in substrate binding. Results showed that, while not the major product, the inverted product was detected via chiral GCMS. Secondly, it is shown that all three cytochrome P450 enzymes (OxyA-C) that catalyse the sequential formation of three essential oxidative cross-links within the chloroeremomycin molecule do so with the retention of the oxygen atom on the peptide backbone and without the incorporation of oxygen in the air. This portion of the work is published in ChemBioChem 2008; 9:2209. The final part of the study was the development of a high-throughput screening method for NRPS A-domains, with the aim of both rapid characterisation and directed evolution of novel substrate specificity. This led to the identification that the amino acid loaded by the first A-domain of the teicoplanin NRPS was shown to load the d-amino acid in preference to the l-amino acid. This is in contrast to the equivalent domain in the chloroeremomycin gene cluster that loads the l-amino acid.
Download: Studies on the biosynthesis of non-ribosomal peptides.