The pharmaceutical industry is no stranger to fermentation. Synthetic biology has been used for the production of both biologic and chemical APIs for decades. While it has not been the predominant method in either sector, the greater sustainability and ability to access novel structures provided by fermentation processes are driving greater interest, particularly for small molecules.

Many advantages of fermentation

Cell culture, while often more suited for the production of biologics, One key reason is that the organisms have faster and more stable growth patterns and lower intrinsic metabolic burden.

In addition, fermentation often involves the conversion of cheap and readily available raw materials (sugar or other cheap substrates) into high-value products with high yields/titers, ensuring the commercially viable manufacture of high-quality products,

Processes typically proceed at room temperature and ambient pressure in water, avoiding the use of harmful or toxic solvents or chemical raw materials and production of dangerous waste.
Synthetic biology can in some cases also provide access to molecules that cannot be produced via traditional synthetic organic chemistry
There are also decades of fundamental research and proven manufacturing success supporting the growing interest and application of synthetic biology and fermentation for chemical API production
The key to realizing all of these benefits, however, Martinelli stresses, is to recognize when synthetic biology provides the optimum solutions—either by providing access to novel structures or higher yields/selectivities—and when organic chemistry is the best approach.

Natural and engineered host strains

microorganisms useful for fermentation into two classes: natural, classic producers and engineered host strains (genetically modified organisms). Classic microorganisms widely used in biotechnology processes include bacteria (Streptomyces sp., Mycobacterium sp., Paracoccus sp.) and fungi (Aspergillus sp., Penicillium sp., Acremonium sp., Tolypocladium inflatum, Claviceps purpurea, Blakeslea sp., etc.).

A focused set of yeasts, such as Saccharomyces cerevisiae and Pichia pastoris (P. Pastoris) and bacteria such as Escherichia coli (E. Coli), make up the second group. “These host strains are selected based on suitability for genetic modifications and utility to efficiently produce APIs and compounds, including many products not practical via fermentation previously,”

Advances in biologic and analytical technologies

A primary driver of recent interest in fermentation is advances in molecular biology and synthetic biology. “These advances allow producer strains to be engineered with greater understanding and effectiveness, which is therefore enabling the development of new processes. They can also be adapted and improved using established fermentation process knowledge and infrastructure that has been built over decades.

Metabolic engineering, therefore, is playing a much greater role because it can be applied to many different goals for continuously improving practical processes. Martinelli agrees that metabolic engineering and genetic engineering play a key role in the development of novel biosynthesis processes because they are crucial to yield enhancement as well as diversity generation. “By rewiring the microbial network, it is possible to drastically divert the flow of material through the cell metabolism and thus achieve production of the target molecule at the desired scale and cost,” he says.

Informatics are crucial, too

Advances in biologic and analytical technologies have occurred in parallel with similar advances in informatics and other digital technologies. Dual development has been necessary to efficiently process the large quantities of data produced and ensure data .

Media Contact:
Mercy
Managing Editor