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TOPCAPI SIGNED

Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

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.

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

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 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.	UK (MANCHESTER)	coordinator	1˙554˙128.00
2	ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO Organization address address: TEHNOLOSKI PARK 21 city: LJUBLJANA postcode: 1000 website: www.aciesbio.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SI (LJUBLJANA)	participant	559˙250.00
3	NAICONS SRL NAICONS SRL Organization address address: VIA GUARAGNA 3 city: SARONNO VA postcode: 20147 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	IT (SARONNO VA)	participant	535˙000.00
4	UNIVERSITY OF YORK UNIVERSITY OF YORK Organization address address: HESLINGTON city: YORK NORTH YORKSHIRE postcode: YO10 5DD website: http://www.york.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.	UK (YORK NORTH YORKSHIRE)	participant	531˙967.00
5	ASOCIACION DE INVESTIGACION INBIOTEC, INSTITUTO DE BIOTECHNOLOGIA DE LEON ASOCIACION DE INVESTIGACION INBIOTEC, INSTITUTO DE BIOTECHNOLOGIA DE LEON Organization address address: AVENIDA REAL 1 PARQUE CIENTIFICO city: LEON postcode: 24006 website: www.inbiotec.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	ES (LEON)	participant	509˙842.00
6	FUNDACION CENTRO DE EXCELENCIA EN INVESTIGACION DE MEDICAMENTOS INNOVADORES EN ANDALUCIA FUNDACION CENTRO DE EXCELENCIA EN INVESTIGACION DE MEDICAMENTOS INNOVADORES EN ANDALUCIA Organization address address: AVDA DEL CONOCIMIENTO 3 city: ARMILLA GRANADA postcode: 18100 website: www.medinaandalucia.es contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	ES (ARMILLA GRANADA)	participant	499˙375.00
7	UNIVERZA V LJUBLJANI UNIVERZA V LJUBLJANI Organization address address: KONGRESNI TRG 12 city: LJUBLJANA postcode: 1000 website: http://www.uni-lj.si contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SI (LJUBLJANA)	participant	449˙425.00
8	EXPLORA SRL EXPLORA SRL Organization address address: Via Giacomo Peroni 386 city: ROMA postcode: 131 website: www.explora-biotech.com contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	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

List of publications.
year	authors and title	journal	last update
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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The information about "TOPCAPI" are provided by the European Opendata Portal: CORDIS opendata.