51cg

Biography

08/2022 -                 Personal Chair, 51cg, UK

08/2018 - 07/2022   Reader, 51cg, UK

08/2014 - 07/2018  Senior Lecturer, 51cg, UK

10/2008 - 07/2014   Lecturer, 51cg, UK 

06/2002 - 09/2008   Postdoctoral fellow, University of St Andrews, UK 

1999 - 2002             Ph.D.   University of Wales Swansea, UK 

Research Overview

My research carries on the great tradition of UK natural product biosynthesis activity. We have  all the required skills to succeed in such an enterprise, involving discovery of new families of specialised metabolites, bacterial genomics, chemical synthesis and the associated molecular biology to manipulate genomes to enzymology and the reconstruction of biochemistry. All of this is focussed on understanding the molecular basis and mechanism of natural products assembly.

Recent contributions involve the understanding of a group of unsaturated amino acids called dehydroamino acids (dhAAs). dhAAs are key components in many peptidyl therapeutics and versatile building blocks in peptide chemistry where organic chemists generate peptidyl derivatives through Michael additions, cross couplings and cycloaddition. They are used as bio-orthogonal handles for later stage modification of biomolecules. However, accessing dhAAs in structurally complex molecules presents a synthetic challenge, often resulting in poor atomic economy.

Among approximately 40 dhAAs found in the natural product inventory, only two, dehydroalanine (Dha) and (Z)-dehydrobutyrine (ZDhb), are well-studied. In this context our lab has elucidated the formation of several understudied dhAAs in newly discovered bacterial peptide-related metabolites, such as pyrrolizidine alkaloids (PAs) (Angew Chem. Int. Ed. 2015, 54, 12697, Nat. Comm. 2022, 13, 62), short dehydrated non-ribosomal peptides (Angew Chemie. Int. Ed. 2021, 60, 3229) and a new family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) (Nat. Comm. 2022, 13, 5044) as shown below. Apart from this, we have also accumulated an outstanding body of work from bioactive natural product discovery to new enzymology as evidenced in our publication profile.

The discovery we made offers an alternative to rational engineering of pathways to generate bioactive peptides. As such we have obtained grants from various funding bodies (i.e. UKRI, Leverhulm Trust, Royal Society, Royal Society of Edinburgh, IBIOIC, EC) to further investigate potential applications of novel enzymes identified in these pathways towards the development of pharmaceuticals. 

Past Research

My team has accumulated a good body of work on bioactive natural product discovery (from polyketides and peptides to alkaloids)  and their biosynthesis, and new enzyme investigation as shown below. Collectively it is a combination of both its range and illustration and  these new organic molecules and new enzymes my team has discovered will find applications for the development of pharmaceuticals and agrochemicals or new ways to biosciences.

Collaborations

Professor Mathew Jenner, Department of Chemistry, University of Warwick, UK

Professor Steven Cobb, Department of Chemistry, University of Durham, UK

Dr Jioji Tabudravu, School of Natural Sciences, University of Central Lancashire, UK

Dr David Clarke, EastChem, School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK

Professor Bruce Milne, Department of Physics, University of Coimbra, Rua Larga, 3004-516, Coimbra, Portugal

Professor Yi Yu, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China

Professor Kwaku Kyeremeh, Department of Chemistry, University of Ghana, Ghana

NCIMB Ltd and Ingenza Ltd

Funding and Grants

We gratefully thank the funding bodies below for financial supports of our research

MRC, BBSRC, Leverhulm Trust, EC, IBIOIC, The Royal Society and The Royal Society of Edinburgh.

Teaching Responsibilities

CM4518 Biological origin of natural products

CM1020 Chemistry for Biosciences 1

CM1512 Chemistry for Biosciences 2

CM3534 Organic and Biological Chemistry