Skip to main content

Refactoring monoterpenoid indole alkaloid production in microbial cell factories

Objective

Plants produce some of the most potent human therapeutics and have been used for millennia to treat illnesses. The monoterpenoid indole alkaloids (MIAs) are plant secondary metabolites that show a remarkable structural diversity and pharmaceutically valuable biological activities with more than 2,000 MIAs derived from the common precursor strictosidine. However, because most MIA chemicals do not have their biosynthetic pathways elucidated and MIA-producing plants are not genetically trackable, MIAs are under-represented in recently introduced medicines. In the consortium for Refactoring of Monoterpenoid Indole Alkaloids in Microbial Cell Factories (MIAMi) our main objective is to develop sustainable microbial production of new human therapies for the benefit of the European biotech industry, human health, and the environment. To do so, MIAMi will i) develop a new approach for MIA biosynthetic pathway discovery in plants founded on supervised learning algorithms based on omics data sampled from > 20 MIA producing plants, ii) contribute to standardisation of bioengineering by development of SOPs for characterisation of > 100 DNA elements for control of gene expression, protein interactions, and sub-cellular localisation, iii) build a public parts repository and Bio-CAD for forward engineering of compartmentalised biosynthetic pathway designs in yeast, and iv) apply automated genome engineering to prototype > 1,000 new-to-nature MIA biosynthetic pathway designs in order to identify robust designs for scale-up microbial MIA production processes, and evaluate the environmental benefits and risks compared to existing value chains. The excellent, interdisciplinary and inter-sectorial consortium will showcase the use of the new approaches and standardised data inventory to produce both commercially available and new-to-market MIAs rauwolscine, tabersonine and alstonine in yeast, and finally test their bioactivity as new cancer and psychosis treatment drug leads.

Field of science

  • /social sciences/economics and business/economics/production economics
  • /natural sciences/computer and information sciences/artificial intelligence/machine learning/supervised learning

Call for proposal

H2020-NMBP-BIO-2018-two-stage
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

DANMARKS TEKNISKE UNIVERSITET
Address
Anker Engelundsvej 1 Bygning 101 A
2800 Kgs Lyngby
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 438 313,75

Participants (7)

JOHN INNES CENTRE

Participation ended

United Kingdom
EU contribution
€ 0
Address
Norwich Research Park Colney
NR4 7UH Norwich
Activity type
Research Organisations
UNIVERSITE DE TOURS
France
EU contribution
€ 1 165 125
Address
Rue Du Plat D Etain 60
37020 Tours
Activity type
Higher or Secondary Education Establishments
EXPLORA SRL
Italy
EU contribution
€ 719 250
Address
Via Giacomo Peroni 386
00131 Roma
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
FUTURE GENOMICS TECHNOLOGIES BV
Netherlands
EU contribution
€ 853 750
Address
Sylviusweg 74
2333 BE Leiden
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
KOBENHAVNS UNIVERSITET
Denmark
EU contribution
€ 341 116,25
Address
Norregade 10
1165 Kobenhavn
Activity type
Higher or Secondary Education Establishments
AXYNTIS
France
EU contribution
€ 619 375
Address
45 Rue De Pommard
75012 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany
EU contribution
€ 1 511 371,25
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Research Organisations