The novoPT™ technology relies on Biotica's detailed understanding of polyketide biosynthetic pathways
Click here for a presentation summarising novoPT™ lead optimisation
Understanding the polyketide synthase is key
The enzyme responsible for polyketide production is called the Polyketide Synthase (PKS). Biotica’s patented novoPT™ technology takes advantage of the one-to-one correspondence between the genes encoding for the PKS, the PKS enzyme itself and the resulting polyketide. The PKS has a modular structure that enables Biotica to predict how genetic changes translate to changes in the resulting polyketide.
Polyketide ‘assembly line’
When a micro-organism synthesizes a polyketide, the PKS ‘loading module’ selects a chemical called an activated carboxylic acid (ACA). Then multiple PKS ‘extender modules’ each in turn select another ACA and link it to the previous one. When the chain is complete, it is cleaved and usually the ends are joined to form a cyclic compound. Sometimes additional enzymes change the molecule further, for example by adding sugars.
novoPT™ harnesses and extends natural polyketide diversity
The diversity in polyketide structures arises from variation in the number of extender modules in a PKS, selectivity of the loading module and extender modules for different ACAs and other differences such as post-PKS glycosylation.
When using novoPT™ to create novel polyketide therapeutics, Biotica swaps, deletes or adds components of the PKS gene cluster. This results in predictable changes to the PKS enzyme, and therefore to the resulting polyketide. Combining different genetic changes, and sometimes additional semi-synthetic alterations, generates a focused library of diverse compounds from which to select a candidate drug.