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TOPCAPI SIGNED

Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients

Total Cost €

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EC-Contrib. €

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Partnership

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 TOPCAPI project word cloud

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

heterologous    rimosus    acne    cell    synthetic    efficiency    streptomyces    intermediates    6dm    topical    predictive    data    tigecycline    expression    staphylococcus    toolbox    metabolomics    time    polyketide    bacterial    tetracycline    actinomycete    optimise    expanded    industrially    tetracyclines    power    coelicolor    minocycline    natural    experiments    bacteria    fabrication    ge2270    drug    integrating    levels    omadacycline    actinomycetes    starter    industrial    24    asymp    compounds    transcriptomics    compound    biosynthesis    anti    purity    improvement    metabolic    characterised    variants    industry    trials    methicillin    engineer    topcapi    mathematical    nai    clinical    strain    biosynthetic    infections    obtain    factories    biology    resistant    medically    6dm6dh    tc    deshydro    strains    conversion    desmethyl    added    synthesis    aureus    host    engineering    microbial    genome    species    editing    semi    engineered    combined    drive    complete    rapid   

Project "TOPCAPI" 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]
 Project website http://topcapi.eu
 Total cost 5˙063˙361 €
 EC max contribution 5˙063˙361 € (100%)
 Programme 1. H2020-EU.2.1.4. (INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies – Biotechnology)
 Code Call H2020-NMBP-BIO-2016
 Funding Scheme RIA
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF MANCHESTER UK (MANCHESTER) coordinator 1˙554˙128.00
2    ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO SI (LJUBLJANA) participant 559˙250.00
3    NAICONS SRL IT (SARONNO VA) participant 535˙000.00
4    UNIVERSITY OF YORK UK (YORK NORTH YORKSHIRE) participant 531˙967.00
5    ASOCIACION DE INVESTIGACION INBIOTEC, INSTITUTO DE BIOTECHNOLOGIA DE LEON ES (LEON) participant 509˙842.00
6    FUNDACION CENTRO DE EXCELENCIA EN INVESTIGACION DE MEDICAMENTOS INNOVADORES EN ANDALUCIA ES (ARMILLA GRANADA) participant 499˙375.00
7    UNIVERZA V LJUBLJANI SI (LJUBLJANA) participant 449˙425.00
8    EXPLORA SRL IT (ROMA) participant 424˙372.00

Map

 Project objective

TOPCAPI will exploit the natural fabrication power of actinomycetes as microbial cell factories to produce three high value compounds: GE2270, a starter compound for the semi-synthesis of NAI-Acne, a new topical anti-acne drug in Phase II clinical trials; 6-desmethyl-tetracycline (6DM-TC) and 6-desmethyl 6-deshydro tetracycline (6DM6DH-TC), intermediates for semi-synthetic conversion to medically important type II polyketide tetracyclines (TC), e.g. minocycline, tigecycline, and the novel omadacycline, which is in Phase III clinical trials, to be used against Methicillin-resistant Staphylococcus aureus infections. Our work will focus on two bacterial host species: Streptomyces coelicolor and Streptomyces rimosus. These host species will be characterised using systems biology approaches, applying integrated data analysis to transcriptomics and metabolomics experiments, combined with predictive mathematical modelling to drive the rapid improvement of these microbial cell factories for industrial drug production using advanced metabolic and biosynthetic engineering approaches. At the same time, we will establish an expanded toolbox for the engineering of actinomycete bacteria as cell factories for other high added-value compounds.

In the proposed 4-year project, we will:

1. Host engineer two new actinomycete strains for industry-level improved heterologous compound production through integrating systems biology-driven strain design and state-of-the-art genome editing.

2. Engineer the biosynthesis pathways to obtain high-efficiency synthesis of GE2270 and new pathway variants for 6DM-TC and 6DM6DH-TC as well as improve its production purity.

3. Optimise the expression of the engineered target pathways in pre-engineered strains to achieve industrially viable production levels of ≈1 g/L for GE2270 and ≈24 g/L for 6DM-TC, while creating a complete novel production strain for 6DM6DH-TC.

 Deliverables

List of deliverables.
Project manager appointed Other 2020-01-31 09:56:14
TOPCAPI Website Websites, patent fillings, videos etc. 2020-01-31 09:56:14

Take a look to the deliverables list in detail:  detailed list of TOPCAPI deliverables.

 Publications

year authors and title journal last update
List of publications.
2019 Francesco Del Carratore, Kamila Schmidt, Maria Vinaixa, Katherine A. Hollywood, Caitlin Greenland-Bews, Eriko Takano, Simon Rogers, Rainer Breitling
Integrated Probabilistic Annotation: A Bayesian-Based Annotation Method for Metabolomic Profiles Integrating Biochemical Connections, Isotope Patterns, and Adduct Relationships
published pages: 12799-12807, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.9b02354
Analytical Chemistry 91/20 2020-02-04
2019 Emmanuele Severi, Gavin H. Thomas
Antibiotic export: transporters involved in the final step of natural product production
published pages: 805-818, ISSN: 1350-0872, DOI: 10.1099/mic.0.000794
Microbiology 165/8 2020-02-04
2019 Francesco Del Carratore, Konrad Zych, Matthew Cummings, Eriko Takano, Marnix H. Medema, Rainer Breitling
Computational identification of co-evolving multi-gene modules in microbial biosynthetic gene clusters
published pages: , ISSN: 2399-3642, DOI: 10.1038/s42003-019-0333-6
Communications Biology 2/1 2020-02-04
2018 Adam Amara, Eriko Takano, Rainer Breitling
Development and validation of an updated computational model of Streptomyces coelicolor primary and secondary metabolism
published pages: , ISSN: 1471-2164, DOI: 10.1186/s12864-018-4905-5
BMC Genomics 19/1 2020-01-31

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