Skip to main content

Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients

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.

Field of science

  • /natural sciences/biological sciences/microbiology/bacteriology
  • /medical and health sciences/basic medicine/pharmacology and pharmacy
  • /engineering and technology/industrial biotechnology/metabolic engineering
  • /natural sciences/computer and information sciences/data science/data analysis

Call for proposal

H2020-NMBP-BIO-2016
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

THE UNIVERSITY OF MANCHESTER
Address
Oxford Road
M13 9PL Manchester
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 554 128,75

Participants (7)

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