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enzC-Hem SIGNED

Creating Versatile Metallo-Enzyme Environments for Selective C-H Activation Chemistry: Lignocellulose Deconstruction and Beyond

Total Cost €

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EC-Contrib. €

0

Partnership

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 enzC-Hem project word cloud

Explore the words cloud of the enzC-Hem project. It provides you a very rough idea of what is the project "enzC-Hem" about.

biocatalysts    small    precise    accessible    ing    strategies    organic    platform    bonds    greener    hem    revealing    functionalizations    optimized    modern    complexes    throughput    engineering    severely    biofuel    molecular    versatile    chemical    chemicals    catalysts    transition    systematically    evolution    catalytic    directed    alphabet    industry    chemically    profiles    stage    revolutionize    streamlined    code    merges    determined    routes    perfectly    limiting    genetic    substrate    alter    orientation    co    supporting    tuned    ultra    programmed    transformations    impressive    molecule    noble    broad    install    molecules    proteins    recognition    amino    global    activation    lignocellulose    protein    aspirational    augmented    enzc    laboratory    synthetic    biotechnology    site    expanded    enzyme    environments    individual    ligands    chemistry    gt    nature    precisely    readily    variants    scaffolds    twenty    catalyst    yielding    metal    ordination    bioactive    functionalize    selectivity    acid    limited   

Project "enzC-Hem" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF MANCHESTER 

Organization address
address: OXFORD ROAD
city: MANCHESTER
postcode: M13 9PL
website: www.manchester.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country United Kingdom [UK]
 Total cost 1˙492˙424 €
 EC max contribution 1˙492˙424 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2022-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF MANCHESTER UK (MANCHESTER) coordinator 1˙492˙424.00

Map

 Project objective

The availability of a versatile catalytic platform to precisely target and functionalize individual C-H bonds in complex organic molecules would revolutionize our synthetic strategies, leading to streamlined routes to high value chemicals and supporting the development of a ‘greener’ chemical industry. Although an impressive range of C-H functionalizations can be achieved with small transition metal complexes, site selectivity is often determined by features of the substrate, and not by the catalyst. A general approach to achieve the more aspirational ‘catalyst controlled’ transformations requires molecular recognition elements within the catalyst which: a) allow precise substrate orientation and b) can be tuned to alter selectivity. In principle, these requirements could be perfectly addressed by protein catalysts which can be readily adapted via laboratory evolution. However, enzyme engineering strategies are currently limited to Nature’s twenty amino acid alphabet, severely limiting the range of metal co-ordination environments, and thus catalytic activities, that are accessible within proteins. In enzC-Hem, I will exploit advanced protein engineering technology available in my laboratory to install ‘chemically programmed’ ligands and/or noble metal co-factors into selected enzyme scaffolds. I will show that the resulting C-H activation catalysts can be systematically optimized via directed evolution with an expanded genetic code using modern ultra-high throughput methods (>100 variants per second), yielding biocatalysts with augmented selectivity/activity profiles. Thus my approach merges the broad range of C-H functionalizations accessible with small molecule catalysts with precise control of selectivity provided by proteins. The biocatalysts developed will address major global challenges in biotechnology and synthetic chemistry, from enhancing lignocellulose derived biofuel production to revealing novel bioactive molecules via late-stage functionalizations.

 Publications

year authors and title journal last update
List of publications.
2018 Moritz Pott, Takahiro Hayashi, Takahiro Mori, Peer R. E. Mittl, Anthony P. Green, Donald Hilvert
A Noncanonical Proximal Heme Ligand Affords an Efficient Peroxidase in a Globin Fold
published pages: 1535-1543, ISSN: 0002-7863, DOI: 10.1021/jacs.7b12621
Journal of the American Chemical Society 140/4 2019-08-29
2018 Takahiro Hayashi, Donald Hilvert, Anthony P. Green
Engineered Metalloenzymes with Non‐Canonical Coordination Environments
published pages: 11821-11830, ISSN: 0947-6539, DOI: 10.1002/chem.201800975
Chemistry – A European Journal 24/46 2019-08-29
2019 Ashleigh J. Burke, Sarah L. Lovelock, Amina Frese, Rebecca Crawshaw, Mary Ortmayer, Mark Dunstan, Colin Levy, Anthony P. Green
Design and evolution of an enzyme with a non-canonical organocatalytic mechanism
published pages: 219-223, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1262-8
Nature 570/7760 2019-08-29
2018 Jin Xu, Anthony P. Green, Nicholas J. Turner
Chemo-Enzymatic Synthesis of Pyrazines and Pyrroles
published pages: 16760-16763, ISSN: 1433-7851, DOI: 10.1002/anie.201810555
Angewandte Chemie International Edition 57/51 2019-08-29

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