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ProgrES SIGNED

Programmable Enzymatic Synthesis of Bioactive Compounds

Total Cost €

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EC-Contrib. €

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Partnership

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 ProgrES project word cloud

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

complexity    bioinformatics    platform    cascade    prior    building    unprecedented    structural    chemical    library    biocatalyst    catalysed    activation    biosynthesis    molecular    biosynthetic    breakthrough    parallel    progres    analytical    transdisciplinary    biocatalytic    lack    simultaneously    generate    monooxygenases    free    de    cascades    mass    proof    found    automated    mediated    away    reactions    intermediates    synthetic    databases    stage    chemo    reaction    sugars    label    organic    limited    manual    catalysts    selective    bottleneck    few    natural    spectrometry    biocatalysts    imino    mostly    enzymes    synthesis    programmable    pharmacopeia    scaffolds    moving    generating    diverse    match    enzymatic    resolution    toolkit    identification    linked    protein    demands    timescale    biology    diversity    tools    functionalisation    group    bottlenecks    engineering    throughput    introducing    nature    therapeutic    bed    diversification    novo    demonstrated    becomes   

Project "ProgrES" 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.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙399˙831 €
 EC max contribution 2˙399˙830 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-07-01   to  2023-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF MANCHESTER UK (MANCHESTER) coordinator 2˙399˙830.00

Map

 Project objective

Enzymes are now established as highly selective biocatalysts in organic synthesis with the range of catalysts and reactions rapidly increasing through access to large protein databases and high-throughput molecular biology tools for biocatalyst engineering. The diversity of biocatalytic reactions is now at a stage where they can be linked in (chemo)-enzymatic reaction cascades, where two or more chemical and/or enzymatic reactions can be catalysed simultaneously generating de novo biosynthetic pathways for chemical synthesis not found in Nature. These reaction cascades have demonstrated important prior art, however they have been mostly limited to few steps and lack the complexity provided by the natural pharmacopeia. ProgrES aims to achieve a step-change by introducing unprecedented structural complexity into de novo pathways and by moving away from manual to automated, high-throughput cascade design and implementation. The proposal is to use a transdisciplinary approach that addresses three important bottlenecks: i. Identification of enzymatic reactions that allow early functionalisation and late stage diversification of the cascade toolkit to increase structural complexity, building on C-H activation mediated by monooxygenases, which are well established in our research group. ii. As diversity of targets increases, high resolution structural analysis of pathway intermediates and products becomes a bottleneck, which is addressed by high-throughput label free mass spectrometry based analytical tools that will match the demands on timescale and numbers. iii. In parallel, we will establish bioinformatics tools adapted from both chemical synthesis and biosynthesis, to allow programmable enzymatic synthesis for cascade design. As proof-of-concept and test bed for the ProgrES platform we aim to generate a library of diverse synthetic imino sugars. This proposal will lead to a major breakthrough in creating a diverse range of scaffolds of therapeutic interest.

 Publications

year authors and title journal last update
List of publications.
2019 Sebastian C. Cosgrove, Ashley P. Mattey, Michel Riese, Michael R. Chapman, William R. Birmingham, A. John Blacker, Nikil Kapur, Nicholas J. Turner, Sabine L. Flitsch
Biocatalytic Oxidation in Continuous Flow for the Generation of Carbohydrate Dialdehydes
published pages: 11658-11662, ISSN: 2155-5435, DOI: 10.1021/acscatal.9b04819
ACS Catalysis 9/12 2020-03-05
2019 Jack Manning, Michele Tavanti, Joanne L. Porter, Nico Kress, Sam P. De Visser, Nicholas J. Turner, Sabine L. Flitsch
Regio‐ and Enantio‐selective Chemo‐enzymatic C−H‐Lactonization of Decanoic Acid to ( S )‐δ‐Decalactone
published pages: 5724-5727, ISSN: 0044-8249, DOI: 10.1002/ange.201901242
Angewandte Chemie 131/17 2020-03-05
2019 Nicholas J. Weise, Prasansa Thapa, Syed T. Ahmed, Rachel S. Heath, Fabio Parmeggiani, Nicholas J. Turner, Sabine L. Flitsch
Bi‐enzymatic Conversion of Cinnamic Acids to 2‐Arylethylamines
published pages: 995-998, ISSN: 1867-3880, DOI: 10.1002/cctc.201902128
ChemCatChem 12/4 2020-03-05

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