Optimizing the synthesis of rare, low-concentrated and complex chemical compounds
Once a biologically active metabolite has been identified, its production needs to be optimized, either in the strain where it was originally found, or in a domesticated chassis strain for which a series of genetic engineering tools are already available. The chosen strain is then genetically modified to redirect its metabolism into gradually producing increasing amounts of the compound, while fermentation conditions are also improved to attain levels that are compatible with production at an industrial scale. The optimized process is the used during the production phases performed under GLP (Good Laboratory Practices) and GMP (Good Manufacturing Practices) conditions to manufacture pilot batches for in vivo assays and produce the drug on a large-scale.
Technologies at work
Measure and quantify the active metabolite across all the steps of the process.
Engineer the gene cluster responsible for the synthesis of a metabolite in the strain where it was discovered, or in a related microbial factory, to gradually optimize compound biosynthesis.
Analyze the organization of the bacterial genome to identify critical genetic elements that influence the biosynthesis of the compound to guide the synthetic biology step. Follow and document the optimization process.
Determine the optimal grow conditions to enhance production of the active compound and ensure their transferability to an industrial scale.
Scale up the purification process of the active metabolite and proceed to its formulation (the selection of excipients that enter into the final composition of the drug according to the chosen route of administration).