Directing Biosynthesis VI

We are having a great time at Directing Biosynthesis VI in Edinburgh presenting our recent research and enjoying some fantastic talks including an excellent lecture from our very own Wei li Thong

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Check out this short video

Want to see what a typical day in our lab looks like. Meet members of our group having fun, planning, executing and presenting their exciting research!

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Super pleased to Welcome four new postdocs to our lab:

Prof Dongxu Jia studied for his PhD at Jiangnan University in the field of fermentation engineering. He now works at the Zhejiang University of Technology as an associate professor and joins us as a visiting researcher with a CSC fellowship

Dr Guangcai Xu trained in biochemistry at Xi’an Jiaotong and the University of Liverpool. He worked in industrial biocatalysis at Suzhou before completing his PhD at the University of Groningen.

Dr Remi Zallot obtained his doctorate degree from Université de Bordeaux, held PDRA positions at University of Florida, University of Illinois at Urabana-Champaign and a Marie Curie Individual Fellowship at Swansea University

Dr Andreea Iorgu received her BEng in Chemical Engineering and MEng in Advanced Materials from Politehnica University of Bucharest before studying for a PhD in Biophysical Chemistry at the University of Manchester. She continued her research in Sam Hay’s group and joins the group as a PDRA.

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Warm welcome to two of the most recent PhD students to join our lab:

Aimee received her MChem degree from the University of Manchester. Continuing in Manchester, Aimee joined the iCAT CDT. She has previously completed project rotations with the Procter and the Bures group

Kehan studied for an MChem in Chemistry at the University of Manchester having undertaken internships at Nanjing Tech University, Suzhou university and Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences

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RSC Interdisciplinary Prize (2022).

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/

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3rd Synthetic Biology of Natural Products Conference

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!

   

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Check out our labs work on Merging enzymes with chemocatalysis for amide bond synthesis

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

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A very warm welcome to the new PhD students that joined out group 2021/2022

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.

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Our teams latest paper is out in Nature Communications

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:

https://www.manchester.ac.uk/discover/news/manchester-scientists-produce-new-antibiotics-by-gene-editing/

And another story with more details from the Nature web site:

https://microbiologycommunity.nature.com/posts/gene-editing-enables-rapid-engineering-of-complex-antibiotic-assembly-lines

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Our labs latest paper is in Nature.

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.

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