Developing a plant protein with great taste
- Goal: to provide a low-calorie, plant-based, high potency sweetener as a sugar substitute
- Origin: edible plant
- Size: 6.5 kDa
- Host: Pichia pastoris
- Status: developmental
- Partner: open
To demonstrate the power and versatility of the precision fermentation approach, we used microbial fermentation to produce three model proteins of potential value for human nutrition.
These protein examples come from a plant, an animal and from a probiotic gut bacterium respectively. As every microbial platform has its preferences when it comes to expressing proteins, we took advantage of our own range of production platforms to choose the ones best suited.
Having identified a desirable protein of choice that matches a list of criteria including functionality, safety and nutritional value, the next key step is selecting a matching microbial production host from our range of platforms.
Our production hosts are the result of continuous improvement programs at BRAIN involving a genetic toolbox, proprietary genome editing and a wealth of experience.
Promising initial productivities seen for a target protein are further improved by developing suitable fermentation and downstream processes. These need to match requirements for cost-efficient production when scaled up to commercial scale at our ISO-certified production plant or a selected toll manufacturer.
Every microbial expression platform has its performance characteristics, strengths and weaknesses. It is therefore critical to select the right platform that matches specific requirements for a given target protein.
Production strains are selected from bacteria (E. coli, Bacillus), yeasts (Pichia, Yarrowia) and filamentous fungi (Aspergillus). Depending on provenance and category of the target protein in question, an initial host screening will be performed to determine preferable choices from BRAIN’s range of platforms.
The development of a microbial production host targets its biosynthetic machinery, which is critical in defining its performance as an efficient protein producer. Complex cellular processes governing gene expression, protein folding, secretion and stability involve an array of factors that may need to be introduced or improved. Our experience in setting up expression systems, a comprehensive genetics toolbox and our proprietary genome editing system are key to achieving these goals.
Gene expression and protein secretion are natural processes of microbial physiology determined by the cell’s genetic setup, available nutrients and environmental stimuli. Critical parameters for a fermentative production process therefore include growth media composition, feeding rates, agitation and aeration, all of which require careful monitoring and adjustment to ensure process productivity.
Scaling up a microbial fermentation process for protein production from lab scale to commercial production can literally mean moving from drop volumes to swimming pool dimensions of controlled fermentation media, with living cells that need to be kept happy and productive.
Within the BRAIN Biotech Group we are equipped to perform submerged fermentation up to the 10 cbm scale using ISO-certified equipment and processes. We have established partnerships for going larger.