DOMINOES : Design of new enzymes for the biosynthesis of innovative amino acids and peptides
Domain Health and wellbeing
It has been over 50 years since a marketing authorization (MA) was filed for a treatment targeting Gram-negative pathogens.
Polymyxins of bacterial origin:
Used to develop commercial antibiotic treatments (Colimycin), they have known advantages in terms of production quantity/cost and deadlines. However, antibiotic resistances are developing, making these treatments ineffective.
Antibiotic potentiators are emerging, but their complex chemical synthesis remains difficult to adapt on an industrial scale. In addition, some of these molecules require the synthesis of rare amino acids which are not currently available on the market.
As a result, current antibiotics are becoming less and less effective and there is no accessible and industrial alternative for resistant patients.
It is a bacterial bioproduction solution of polymyxin-like peptide molecules. Their improved pharmacological properties make it possible to produce antibiotics that develop less resistance for patients.
- New anti-infectious molecules,
- Innovative peptide and rare amino acid production for anticancerous molecule, antibiotics, anti-infectious molecule, immunosuppressors and other active peptides.
- Bioproduction of antibiotic potentiator to molecules at controlled cost
- Known producing microorganisms directly compatible with well-established industrial processes
- Simplification of peptide production by chemical means with the production of rare molecular building blocks such as D-DAB
- Opening up new synthesis pathways for chemical peptides through the provision of rare amino acids
How it works
Based on the control of the biosynthesis pathway of a given polymyxin, our solution uses peptide chemical derivatives as a model to redirect the production of the polymyxin. In order to provide:
- Rare amino acids necessary to manufacture innovative peptides (anticancer, antibiotics, antifungal) such as: D-2,4-diaminobutyric acid (DAB), other D-series amino acids and non-proteinogenic amino acids.
- Peptide-like compounds using these amino acids based on a non-chemical process and active against antibiotic-resistant bacteria.
By using directly compatible microorganisms, its implementation can be adapted to existing industrial processes without impacting costs and production.
This project will take place at LIENSs laboratory of La Rochelle University within the CNRS 7266 Environment and Societies UMR and more specifically in the BCBS team: Biotechnologies and Chemistry of Bio-resources for Health.
1 patent : WO2015111013
(TRL : 4)
- The gene cluster responsible for the synthesis of polymyxin E in a strain of Paenibacillus has been cloned, sequenced and its operation has been described. Our patent protects these sequences and their use for biotechnological purposes.
- In order to carry out the biosynthesis of innovative derivatives inspired by natural polymyxins we will modify the synthetases of polymyxin E. The cloning of the various genes coding for the synthetases and their modules has already been carried out.
- The regions to be edited in order to redirect the syntheses towards those of the derivatives generated by the chemists have been identified and cloned.
- As POC for 2021, we build bioprototype able to produce a polymyxine derivate designed and produced today in chemical way
- It is proposed to make derivatives of polymyxins to order
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