DOMINOES : Design of new enzymes for the biosynthesis of innovative amino acids and peptides

Challenges

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.

Promising molecules:

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.

Innovative solution

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.

Competitives advantages

• 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:

1. 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.
2. 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.