Since the discovery of recombinant DNA technology, several types of microbes have been established as a versatile biomolecule expression system. This can be attributed to the ease of handling of microbial cell lines, which are considered less fragile (compared to cells of higher eukaryotes); rendering them a popular choice for manufacturing operations. Moreover, incremental evolution of the concept of microbial fermentation have facilitated various advancements in development and improvement of microbe-based manufacturing technologies. Presently, there are a number of traditional and innovative microbial expression systems / platforms, which are used for manufacturing a variety of biologics and small molecules.
What are the key differences between microbial and mammalian expression systems?
There are several expression systems, such as mammalian, microbial, insect and plant cell-based systems; however, amongst these, mammalian and microbial expression systems are the most prominent.
Mammalian Expression Systems
Microbial Expression Systems
Ease of working with cells
Their fragile nature makes these systems difficult to handle
Comparatively easier to work with / handle
Ease of culturing cells
Culturing of mammalian cells is a difficult process and requires expertise
Comparatively easier to culture and do not require highly skilled personnel
Transfection is primarily done via liposome mediated transfection, electroporation and microinjection
Transfection is done mainly through heat shock method
Post-translation modifications occur within the cell
Post-translational modification is required to be done in an additional step after the release of protein / product
Preservation of native structure
Antibody produced will be relatively closer to its native structure
Antibodies can be expressed; however, their similarity to native structure is low
Chinese hamster ovary (CHO) cells, baby hamster kidney (BHK) cells, human embryonic kidney (HEK) cells, and the WI-38 and MRC-5 cell lines (derived from fetal cells)
Bacterial expression systems: Escherichia coli, Salmonella typhimurum, Vibrio cholerae and Bacillus brevis Yeast expression system: Saccharomyces cerevisiae and Pichia pastoris
What is the outsourcing trend?
Over the years, the outsourcing trends for manufacturing activities have been increased with an annualized rate of 4%. It is worth noting that, since 2018 the outsourcing activities for microbial manufacturing has expediated from 60% to 70%, approximately. The current pandemic seems to have no significant impact on the outsourcing activity, in contrast there is an increased demand for the production of biologics for the treatment of COVID-19. Moreover, once the pandemic subsidies, prioritization of the outsourced projects will form the part of new normal. Below are the list of some advantages and disadvantages associated with microbial manufacturing.
What are the recent initiatives undertaken by Microbial CMOs, to combat COVID-19?
In the past few months, the microbial CMOs have undertaken various collaborative initiatives, to develop vaccines / biologics as the potential therapeutic against COVID-19. For instance, Cytovance Biologics have signed a process development and manufacturing agreement with Akshaya Bio, to upscale the production of the therapeutic vaccine against COVID-19 using Cytovance’s GMP insect cell microbial manufacturing platform.
Microbial fermentation has already proved their potential in the biopharmaceutical industry. Moreover, the innovation and adoption of novel fermentation technologies have significantly brought down the cost of manufacturing. Having said that, we are laid to believe that microbial fermentation will provide lucrative business opportunities in the coming decade.
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