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Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients

Obiettivo

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.

Invito a presentare proposte

H2020-NMBP-BIO-2016
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Meccanismo di finanziamento

RIA - Research and Innovation action

Coordinatore

THE UNIVERSITY OF MANCHESTER
Indirizzo
Oxford Road
M13 9PL Manchester
United Kingdom
Tipo di attività
Higher or Secondary Education Establishments
Contributo UE
€ 1 554 128,75

Partecipanti (7)

ASOCIACION DE INVESTIGACION INBIOTEC, INSTITUTO DE BIOTECHNOLOGIA DE LEON
Spagna
Contributo UE
€ 509 842,50
Indirizzo
Avenida Real 1 Parque Cientifico
24006 Leon
Tipo di attività
Research Organisations
FUNDACION CENTRO DE EXCELENCIA EN INVESTIGACION DE MEDICAMENTOS INNOVADORES EN ANDALUCIA
Spagna
Contributo UE
€ 499 375
Indirizzo
Avda Del Conocimiento 3
18100 Armilla Granada
Tipo di attività
Research Organisations
UNIVERZA V LJUBLJANI
Slovenia
Contributo UE
€ 449 425
Indirizzo
Kongresni Trg 12
1000 Ljubljana
Tipo di attività
Higher or Secondary Education Establishments
UNIVERSITY OF YORK
United Kingdom
Contributo UE
€ 531 967,50
Indirizzo
Heslington
YO10 5DD York North Yorkshire
Tipo di attività
Higher or Secondary Education Establishments
EXPLORA SRL
Italia
Contributo UE
€ 424 372,50
Indirizzo
Via Giacomo Peroni 386
00131 Roma
Tipo di attività
Private for-profit entities (excluding Higher or Secondary Education Establishments)
NAICONS SRL
Italia
Contributo UE
€ 535 000
Indirizzo
Via Guaragna 3
20147 Saronno Va
Tipo di attività
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO
Slovenia
Contributo UE
€ 559 250
Indirizzo
Tehnoloski Park 21
1000 Ljubljana
Tipo di attività
Private for-profit entities (excluding Higher or Secondary Education Establishments)