Our group is very pleased that Jason won the RSC Interdisciplinary Prize (2022). “For innovative research spanning organic chemistry to molecular genetics, leading to the discovery, characterisation, and engineering of many novel enzymes.”
Many thanks to our very talented research group for their hard work, dedication and excellent research over the years, which has made this possible!
https://www.rsc.org/prizes-funding/prizes/2022-winners/professor-jason-micklefield/
Wei Li Thong, Katherine Robins & Mike Rowlinson had a great time presenting the labs most recent work at the 3rd Synthetic Biology of Natural Products Conference #SBNP22 in Mexico. Beautiful setting and a fantastic conference. Here they are having fun!
Merging enzymes with chemocatalysis for amide bond synthesis
Amides are one of the most fundamental chemical bonds in nature. In addition to proteins and other metabolites, many valuable synthetic products comprise amide bonds. Despite this, there is a need for more sustainable amide synthesis. Herein, we report an integrated next generation multi-catalytic system, merging nitrile hydratase enzymes with a Cu-catalysed N-arylation reaction in a single reaction vessel, for the construction of ubiquitous amide bonds. This synergistic one-pot combination of chemo- and biocatalysis provides an amide bond disconnection to precursors, that are orthogonal to those in classical amide synthesis, obviating the need for protecting groups and delivering amides in a manner unachievable using existing catalytic regimes. Our integrated approach also affords broad scope, very high (molar) substrate loading, and has excellent functional group tolerance, telescoping routes to natural product derivatives, drug molecules, and challenging chiral amides under environmentally friendly conditions at scale.
For more background see:
https://go.nature.com/3FCmSxf
And for news reports see:
Greener amide bonds in Nature Chem Biol: https://doi.org/10.1038/s41589-022-00988-7
Collaborative catalysis in Nature Reviews Chemistry : https://www.nature.com/articles/s41570-022-00369-7
Enzyme-and-copper combo builds amide bonds via @cenmag: https://cen.acs.org/synthesis/Enzyme-copper-combo-builds-amide/100/i4
Photos from top left: Stuart, Isobel, Sebastian, Sydney, Luke
Stuart Angiolini completed his MChem degree at Heriot-Watt University in 2020. During his degree, he completed a yearlong industrial placement with Fiberlean Technologies in Cornwall, working on development of paper and packaging additives using microfibrillated cellulose. Stuart will be working on merging enzymes with chemocatalysts, giving new routes to make and functionalise molecules.
Isobel Cordrey received her BSc in Biological Sciences (Biotechnology) from the University of Edinburgh. She is now working on synthetic biology approaches for heterologous expression of biosynthetic pathways in Actinobacteria, both in Manchester and at A*STAR in Singapore.
Sebastian Cuesta received his BSc in Chemical Science from Catholic University of Ecuador & an MSc in Drug Discovery and translational Biology from the University of Edinburgh, Scotland. Sebastian will be working on the discovery, characterisation and evolution of new enzymes for antibiotic biosynthesis and nucleic acid therapeutics.
Sydney Flower obtained her MSci in Biochemistry from the University of Birmingham. She will be working on antibiotic synthesis pathways with Jason and genetic engineering for natural product synthesis in Halomonas with Prof Guo-Qiang Chen at Tsinghua University.
Elsa Prendergast from the University of Manchester, UK…
Luke Yates completed his MSci at the University of East Anglia, with a year abroad spent in Australia at the University of Technology Sydney. His project at the MIB involves the discovery, characterisation and engineering of new ligase enzymes for more sustainable amide bond synthesis.
Gene editing enables rapid engineering of complex antibiotic assembly lines
Our most recent paper describes an entirely new route to complex antibiotics exploiting gene editing to re-programme pathways to future medicines urgently required to combat antimicrobial resistance, treat neglected diseases and tackle future pandemics. The paper adopts an highly interdisciplinary approach, combining cutting edge chemistry, microbiology & genetics. Well done to our team for delivering this.
For additional context here is a link to the story posted on the Universities main web site:
And another story with more details from the Nature web site:
The paper is about amide ligase enzymes – from bacterial phytotoxins, natural product biosynthesis, enzyme structure & engineering, to biocatalysis & new routes to drugs for COVID19 etc.
https://www.nature.com/articles/s41586-021-03447-w
https://rdcu.be/ckWgF
For more information see the full news story here.
For more technical details behind the paper see this blog post.
This paper describes a new way of integrating engineered enzymes and cells, with metal catalysis in a single process, telescoping more sustainable routes to drugs and other targets.
https://www.nature.com/articles/s41929-021-00603-3
https://rdcu.be/ckYsL
For more information see the full news story here.
For more technical details behind the paper see this blog post.
A belated, but nonetheless, very warm welcome to our new PhD students for the academic year 2020/21.
Pictured from left to right Jess, Joe & Eloise.
Jessica Logue received her MChem from the University of Lancaster and is now working on discovery, characterisation and engineering new enzymes for more sustainable synthesis.
Joseph Thompson completed his MChem degree at the University of Nottingham and will be working on new routes to nucleic acid therapeutics.
Eloise O’ Connor was awarded BSc in Biochemistry from Imperial College. Eloise will be developing new synthetic biology approaches for re-assembling biosynthetic pathways for heterologous expression in new yeast strains in collaboration with Prof. Patrick Cai.
Delighted to welcome Dr Puja Saha to our group. Puja won a prestigious Royal Society Newton Fellowship to work in our lab.
Previously Puja was IACS Senior Research Fellow & CSIR Junior Research Fellow with Prof. Jyotirmayee Dash at the Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India. Puja obtained a Ph.D. in Biochemistry, from the University of Calcutta, studying I-motif DNA secondary structure in cancer therapeutics. She also received M.Sc.and B. Sc degrees in Microbiology from the University of Calcutta. Puja will be working on developing new enzymatic cascades to deliver new antibiotics urgently required to combat AMR and treat neglected diseases.
Curr Opin Chem Biol Special Issue on Biocatalysis, we edited with @CampopianoGroup is finally out! Many thanks to the authors that contributed.
https://www.sciencedirect.com/science/article/abs/pii/S1367593120300624
https://www.sciencedirect.com/journal/current-opinion-in-chemical-biology/vol/55/suppl/C
Includes our review – Harnessing and engineering amide bond forming ligases for the synthesis of amides
https://www.sciencedirect.com/science/article/abs/pii/S1367593119301486
