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Expert View: How establishing a symbiotic relationship helps to advance fermentation processes.

IngenzaInjector.jpgFermentation is a key capability in bio-technology used in a number of different sectors, including biopharmaceutical and bio-based chemical manufacturing, biofuel production, and the food, drink and agriculture industries. In this guest article from Alison Arnold, Head of Fermentation at Scottish biotechnology and synthetic biology pioneersIngenza, we focus on how the integration of fermentation techniques with scientific activities in the fields of synthetic and analytical chemistry, informatics, molecular genetics and biochemistry is key to the generation, optimisation and scale-up of innovative bio-based solutions. At Ingenza, the fermentation team collaborates closely with other scientists performing strain engineering and chemical synthesis, working seamlessly to address a diverse array of customer demands.

Fermentation plays an important role in a wide range of applications, such as biopharmaceutical and bio-based chemical manufacturing, food, drink and agriculture, and the production of biofuels. At Ingenza, this service has evolved to keep pace with current needs, with the capacity of the fermentation processes expanding considerably to accommodate efficient, scalable bioprocesses for the sustainable manufacture of chemicals, biologics, pharmaceuticals and biofuels.

A gradual evolution…

Ingenza began life as a biocatalysis company, using its expertise in technologies such as molecular biology, fermentation and chemistry to serve pharmaceutical companies. Generally, these companies would request a few grams of an enantiomerically pure, chiral advanced pharmaceutical intermediate (API) for drug development purposes. If the product showed potential, the process would then need to be scaled up to produce a kilo or even a ton of the target material. From a business perspective, while remaining purely in the biocatalysis sector was not sustainable, working in this field had allowed the development of many core competencies and enabling skills that could be transferred to other areas of biotechnology. This led the company to make the transition away from the production of pharmaceutical intermediates, often using third-party fermentation partners, gradually moving towards in-house fermentation on different scales to make processes more sustainable and cost effective.

Realising the full potential…

Alison Arnold, Head of Fermentation at Ingenza.In a drive to diversify its services, Ingenza explored alternative uses for the key technologies underpinning the biocatalysis processes. Other potential host systems including the yeasts Saccharomyces and Pichia were investigated to complement the existing microbial work with E.coli, and a GMP laboratory was established for biopharmaceutical manufacturing. The creation of a GMP facility was the direct result of a biopharmaceutical project to generate a pre-master cell bank using microbial strain construction and fermentation. The successful completion of this project led to enquiries for mammalian cell lines particularly Chinese hamster ovary cells and, ultimately, an additional, completely separate laboratory for mammalian strain engineering was established.

Another area the company began to explore was biofuel production. Bioethanol production relies on the fermentation of a yeast product engineered to minimise the need for extra additives or enzymes. This helps to reduce the cost of ethanol production. In contrast to biopharmaceutical manufacturing, there is no requirement to follow GMP principles when developing strains for bioethanol production. The yeast and carbon source are simply added to huge fermenters, where the bioethanol is generated. The fermentation capacity which had already been scaled up from the 50,000 litres used for biocatalysis was further extended to 2.6 million litres.


A team effort…

Fermentation is just one stage of the overall product development pathway. In the end, success depends heavily on the interaction between each of the teams involved; molecular biology, fermentation and chemistry. At Ingenza (@IngenzaLtd) it is not uncommon for scientists to move from one team to another, broadening their experience and gaining a better understanding of how the different disciplines are inter-related. This in-depth knowledge is a great strength, acting as a bridge between microbiology and synthetic chemistry.

The relationship between the different departments can be likened to that of a football team, with fermentation as the midfield. The process begins with the microbiology group performing strain engineering, producing a cell line that is passed forward to the fermentation team. Expression of the enzyme is then optimised, designing processes that are suitable for scale-up. Once this has been achieved, the chemists the forwards take over, using the enzyme in the synthesis of potential chemical products. It is this seamless collaboration between distinct yet inter-dependent scientific disciplines that enables the generation, optimisation and scale-up of innovative bio-based solutions to address diverse applications.

Summary…

The fermentation process is central to many bio-based processes, and is an essential part of the workflow in the sustainable manufacture of chemicals, biologics, biopharmaceuticals and biofuels. The synergetic relationship between various scientific disciplines lies at the heart of success, helping to advance the development, optimisation and scale-up of fermentation processes.

Bio-Based World News guest postwritten by:Alison Arnold, Head of Fermentation, Ingenza Ltd, Roslin, UK


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