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SHIKIFACTORY100 project aims towards the production of a universe of more than 100 high-added value compounds from the shikimate pathway, a hub in cell metabolism, through the development of an optimized shikimate chassis (based in 3 sub-hubs: Phe, Trp and Tyr) and the proposal and implementation of novel biosynthetic routes exploring enzyme promiscuity to introduce new pathways for the production of known and newly designed compounds.

Project

Chemical synthesis of complex molecules like natural products is often difficult and may be subject to unclear mechanisms, frequently producing undesired by-products or racemic mixtures, while the complexity of some compounds may render them virtually unattainable.

Nature, on the other hand, can provide a wealth of products, but typically at very low concentrations, which makes their extraction process very expensive. Also, product extraction from plants relies on source availability, often leading to steep price fluctuations, and might have high environmental impact. Conversely, microbial production is a well-established process for industrial compounds naturally produced by the hosts or for known compounds with fully characterized biosynthetic pathways.

SHIKIFACTORY100 project aims towards the production of a universe of more than 100 high-added value compounds from the shikimate pathway, a hub in cell metabolism, through the development of an optimized shikimate chassis (based in 3 sub-hubs: Phe, Trp and Tyr) and the proposal and implementation of novel biosynthetic routes exploring enzyme promiscuity to introduce new pathways for the production of known and newly designed compounds.

The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of steps, the intermediates are converted into Aromatic Amino Acids (AAA) and many other aromatic secondary metabolites which are branch points for other metabolic pathways. This pathway holds a very significant commercial interest, with many compounds associated with multi-million euros global market pools.

 

In this project, 3 major vectors (cf. illustration in the cover page) will be innovatively and synergistically integrated:

  • Collection of natural and non-natural reactions and compounds as well as the discovery and ranking of novel pathways for the production of the target compounds.

  • In silico and in vivo design, rapid prototyping for the pathways selected in the previous vector and optimisation efforts toward chassis and advancing production strains.

  • Application and initial upscaling for a subset of compounds and sustainability appraisal.

 

To champion SHIKIFACTORY100 project - and fulfil its ambitious vision - a consortium with some of the most relevant players in Europe has been assembled, covering research leading institutions in computational design and in vivo implementation of pathways and cell factories. 

Partners

SilicoLife
SilicoLife

Braga, Portugal

SilicoLife
SilicoLife designs optimised microorganisms and novel pathways for industrial biotech applications.
EPFL
EPFL

Vaud, Switzerland

EPFL
EPFL was founded in 1969 and has established itself among the world’s best research and teaching institutions.
DTU
DTU

Copenhagen, Denmark

DTU
Technical University of Denmark (DTU) is recognised internationally in the areas of technology and the natural sciences.
EMBL
EMBL

Heidelberg, Germany

EMBL
EMBL is Europe’s flagship laboratory for life sciences.
DSM
DSM

Delft, Netherlands

DSM
DSM is a global science-based company active in health, nutrition and materials.
University of Manchester
University of Manchester

Manchester, United Kingdom

University of Manchester
The University of Manchester is the largest single-site university in the UK, with research strength across all science disciplines.
University of Minho
Uminho

Braga, Portugal

University of Minho
The University of Minho has expertise in the development of algorithms and computational tools for metabolic engineering.
NOVA University of Lisbon
Nova

Lisbon, Portugal

NOVA University of Lisbon
NOVA University Lisbon is the youngest of Lisbon's state Univiersities.
c-LEcta
c-LEcta

Leipzig, Germany

c-LEcta
c-LEcta is specialised on the discovery, optimisation and production of enzymes and the strain engineering for protein and small molecule production
GalChimia
GalChimia

La Coruña, Spain

GalChimia
GalChimia is a service provider focused in the filed of Synthetic Organic Chemistry.
NNFCC
NNFCC

York, United Kingdom

NNFCC
NNFCC has over 14 years of experience in supporting the development of bio-based chemicals and products.
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