The early career academics presenting in the next Peptide and Protein Science online series will be Dr Jack Rowbotham, BBSRC Discovery Fellow, Manchester Institute of Biotechnology and Dr Aniello Palma, Lecturer, University College Dublin.
Date: 01-11-2024
Time: 1:00-2:00 pm
Venue: an online Zoom lecture
Jack Rowbotham, BBSRC Discovery Fellow, Manchester Institute of Biotechnology
https://research.manchester.ac.uk/en/persons/jack.rowbotham
Title: Rewiring metalloenzymes for efficient redox transformations
There is an increasing drive to integrate sustainable biocatalytic processes into the synthesis of industrially relevant compounds. Several barriers to the industrial implementation of biocatalysis arise from the use of nicotinamide cofactors (NAD(P)+ and NAD(P)H). These cofactors are employed ubiquitously to shuttle electrons to drive both reductive transformations (through H- transfer) and oxidative reactions (through O2 activation), however they introduce problems to the reaction engineering (notably in the need to include recycling systems). In contrast, the use of metalloenzymes enables control over electron transfer between catalytic centres, and so reactions can be “re-wired” to mitigate issues associated with the use of NADP+/NADPH. This talk will demonstrate the synthetic utility of “re-wired” electron transfer pathways for both reductive and oxidative biotransformations. Building on previous work in the Vincent group/HydRegen at the University of Oxford, I will briefly discuss how re-wired catalysis can be used to perform isotopic labelling reactions for synthesis of pharmaceutical and analytical compounds.1-3 I will then discuss new results concerning electron transfer in P450 enzymes, known to selectively perform oxygen atom insertion on inactive C-H bonds. Whilst this chemistry is desirable for a range of applications, the native enzymes often fail to deliver sufficient turnover numbers to be used commercially. The talk will report on new insights discovered from working with so-called “self-sufficient” P450s, with enhanced electron transfer characteristics and higher productivities. Parallels between the reductive and oxidative biocatalytic systems will be discussed, and opportunities for future development and wider application will also be highlighted.
References
[1] J. S. Rowbotham et al., Nat. Commun., 2020, 11, 1454.
[2] J. S. Rowbotham et al., ACS Catal., 2021, 11, 2596 – 2904.
[3] J. S. Rowbotham et al., Chem Sci., 2023, 14, 12160-12165.
Aniello Palma, Lecturer, University College Dublin
https://people.ucd.ie/aniello.palma
Title: “Polyproline Helices as Novel Supramolecular Building Blocks”
The rational design of supramolecular constructs using bio-inspired building blocks is an ever-growing research field. In this talk, I will present on overview of our research interests, which focus on the use of polyproline helices as supramolecular building blocks to rationally design responsive materials and supramolecular nano-constructs. I will discuss how this class of peptides can be engineered to self-assemble into responsive peptide frameworks capable of thermal activation, guest-induced dynamic porosity and enantioselective guest inclusion.[1,2] I will also present some of our latest work on the stereoselective synthesis of peptide-based Pd2L4X4 cages and on the divergent supramolecular assembly of these biopolymers into metallo-peptide nanoparticles.[3,4]
References
[1] D. F. Brightwell, G. Truccolo, K. Samanta, E. J. Fenn, S. J. Holder, H. J.
Shepherd, C. S. Hawes, A. Palma, Chem. - A Eur. J. 2022, 28, e202202368.
[2] D. F. Brightwell, G. Truccolo, K. Samanta, H. J. Shepherd, A. Palma, ACS
Macro Lett. 2023, 12, 908–914.
[3] D. F. Brightwell, K. Samanta, J. Muldoon, P. C. Fleming, Y. Ortin, L.
Mardiana, P. G. Waddell, M. J. Hall, E. R. Clark, F. Fantuzzi, A. Palma,
ChemRxiv 2024, DOI 10.26434/CHEMRXIV-2024-WV36K.
[4] D. F. Brightwell, K. Samanta, J. A. Watts, M. W. Fay, A. Palma, Chemrxiv
2024, DOI 10.26434/CHEMRXIV-2024-FR95J.
For upcoming series, please visit the RSC PPSG website.
If you would like to present in future seminars, please contact one of the organisers.
Rachel Dickman: rachael.dickman.13@ucl.ac.uk
Lucia Lombardi: l.lombardi@imperial.ac.uk
Louis Luk: lukly@cardiff.ac.uk
Date: 01-11-2024
Time: 1:00-2:00 pm
Venue: an online Zoom lecture
Jack Rowbotham, BBSRC Discovery Fellow, Manchester Institute of Biotechnology
https://research.manchester.ac.uk/en/persons/jack.rowbotham
Title: Rewiring metalloenzymes for efficient redox transformations
There is an increasing drive to integrate sustainable biocatalytic processes into the synthesis of industrially relevant compounds. Several barriers to the industrial implementation of biocatalysis arise from the use of nicotinamide cofactors (NAD(P)+ and NAD(P)H). These cofactors are employed ubiquitously to shuttle electrons to drive both reductive transformations (through H- transfer) and oxidative reactions (through O2 activation), however they introduce problems to the reaction engineering (notably in the need to include recycling systems). In contrast, the use of metalloenzymes enables control over electron transfer between catalytic centres, and so reactions can be “re-wired” to mitigate issues associated with the use of NADP+/NADPH. This talk will demonstrate the synthetic utility of “re-wired” electron transfer pathways for both reductive and oxidative biotransformations. Building on previous work in the Vincent group/HydRegen at the University of Oxford, I will briefly discuss how re-wired catalysis can be used to perform isotopic labelling reactions for synthesis of pharmaceutical and analytical compounds.1-3 I will then discuss new results concerning electron transfer in P450 enzymes, known to selectively perform oxygen atom insertion on inactive C-H bonds. Whilst this chemistry is desirable for a range of applications, the native enzymes often fail to deliver sufficient turnover numbers to be used commercially. The talk will report on new insights discovered from working with so-called “self-sufficient” P450s, with enhanced electron transfer characteristics and higher productivities. Parallels between the reductive and oxidative biocatalytic systems will be discussed, and opportunities for future development and wider application will also be highlighted.
References
[1] J. S. Rowbotham et al., Nat. Commun., 2020, 11, 1454.
[2] J. S. Rowbotham et al., ACS Catal., 2021, 11, 2596 – 2904.
[3] J. S. Rowbotham et al., Chem Sci., 2023, 14, 12160-12165.
Aniello Palma, Lecturer, University College Dublin
https://people.ucd.ie/aniello.palma
Title: “Polyproline Helices as Novel Supramolecular Building Blocks”
The rational design of supramolecular constructs using bio-inspired building blocks is an ever-growing research field. In this talk, I will present on overview of our research interests, which focus on the use of polyproline helices as supramolecular building blocks to rationally design responsive materials and supramolecular nano-constructs. I will discuss how this class of peptides can be engineered to self-assemble into responsive peptide frameworks capable of thermal activation, guest-induced dynamic porosity and enantioselective guest inclusion.[1,2] I will also present some of our latest work on the stereoselective synthesis of peptide-based Pd2L4X4 cages and on the divergent supramolecular assembly of these biopolymers into metallo-peptide nanoparticles.[3,4]
References
[1] D. F. Brightwell, G. Truccolo, K. Samanta, E. J. Fenn, S. J. Holder, H. J.
Shepherd, C. S. Hawes, A. Palma, Chem. - A Eur. J. 2022, 28, e202202368.
[2] D. F. Brightwell, G. Truccolo, K. Samanta, H. J. Shepherd, A. Palma, ACS
Macro Lett. 2023, 12, 908–914.
[3] D. F. Brightwell, K. Samanta, J. Muldoon, P. C. Fleming, Y. Ortin, L.
Mardiana, P. G. Waddell, M. J. Hall, E. R. Clark, F. Fantuzzi, A. Palma,
ChemRxiv 2024, DOI 10.26434/CHEMRXIV-2024-WV36K.
[4] D. F. Brightwell, K. Samanta, J. A. Watts, M. W. Fay, A. Palma, Chemrxiv
2024, DOI 10.26434/CHEMRXIV-2024-FR95J.
For upcoming series, please visit the RSC PPSG website.
If you would like to present in future seminars, please contact one of the organisers.
Rachel Dickman: rachael.dickman.13@ucl.ac.uk
Lucia Lombardi: l.lombardi@imperial.ac.uk
Louis Luk: lukly@cardiff.ac.uk
