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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. €

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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.

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

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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fax: n.a.

 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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