Choosing the right strain optimisation strategy: What key factors are critical to success?

The opportunities that RTOs and CDMOs bring

I speak with lots of different companies developing alternative protein solutions and for many, their initial focus is on optimising their strains to improve the yield and productivity of the molecule they’re trying to produce. Most of these companies do this in-house but I would argue that there’s a role for research and technology organisations (RTOs) and contract development and manufacturing organisations (CDMOs) to support. 

The expertise available within RTOs and CDMOs is vast. Having access to staff with deep knowledge and experience of microbial strain development to support projects of this type is really valuable. Plus, understanding the key considerations across the scale-up journey is incredibly useful to companies starting out on this journey, as that expertise may not be available in-house. This support can drastically cut the time of this first stage in the innovation journey and raise confidence in your production process. 

It’s well known in the industry that the ability to scale up the production of alternative proteins using commercially viable processes is critical to not only the success of the company developing the technology, but also to the long-term success of the global alternative proteins market. 

Considering precision fermentation?

The use of precision fermentation to produce dairy proteins and other animal proteins is an expanding field that has potential benefits over traditional farming in terms of reduced land and water use and a lower carbon footprint. In addition, precision fermentation does not require the use of any animal products, so the proteins produced are suitable for vegan diets. 

One of the key stages in developing a precision fermentation process is selecting a suitable microorganism as a host to produce the protein of interest at an industrial scale. Most companies and academics that I speak with who are active in this field use model organisms, such as E. coli, when developing a process. One drawback of using E. coli and other model organisms, such as S. cerevisiae, is that they may not be suitable hosts for processes at a commercial scale. 

My best advice for companies working on alternative proteins is always to think of the end goal in mind and focus your R&D activities on that goal. My job at CPI isn’t to help companies develop the best lab-scale process using a model organism, it’s to get companies to a point where they have a commercially viable, robust process at an industrially relevant scale – and the end process may end up looking very different from where companies started from! With that in mind, I’m happy to share some insights I use when talking to companies who want to scale up. 

There are numerous factors to consider when choosing a suitable host for industrial production, especially when producing an alternative protein intended to enter the food supply chain. 

My top 5 considerations when choosing the right host strain:

1. Regulatory and safety: Has my host strain got any regulatory hurdles or potential issues with safety?

The pathway to regulatory approval of any novel food process is long and complex, so using a microbial host that has no previous history of food use increases the risk and complexity of the regulatory process. 

2. Scalability of fermentation: Is my organism suitable for scale? 

Understanding the history of large-scale processes with the host strain is important. It’s worthwhile ensuring that the strains used are genetically stable and have been assessed for use in continuous fermentation processes. 

3. Downstream processing: Can I isolate the product out of the fermenter easily? 

Precision fermentation products must be produced in high yield and to a high level of purity to enter the food supply chain. Selecting a strain capable of efficient secretion of the product is important to reduce the complexity of the initial harvest material and to simplify the number of downstream processing steps required. 

4. Overall cost of manufacturing: How will my host strain contribute to the economic viability of my process? 

The characteristics of the host strain have a big impact on the techno-economics of the process. Key areas to consider are feedstock quality and costs, product titres, strain productivity, yields and batch times. Simplicity of downstream processing operations also impact greatly on the cost of production. 

5. Ease of genetic manipulation: How easy is my host to manipulate? 

Development of strains for precision fermentation processes need to undergo the familiar design, build, test, learn cycle often associated with engineering biology. The use of established genetic tools will shorten the time needed to generate strains suitable for production at scale.

At CPI, we support customers to reduce the risk involved with the development of new products and processes using biomass, precision and gas fermentation. Many of these processes come to CPI as non-optimised and we help to provide customers with a process that is scalable, economically viable and produces the product of interest in the highest possible yield and purity. 

Our host strain development team can advise on the steps required to achieve these outcomes using appropriate host strains. Get in touch for your free strain optimisation consultation.