Specialty enzymes for niche markets

With its One-BioProducts strategy, first announced at the start of 2023, BRAIN Biotech has started to evolve into an international multi-niche enzyme champion. What does this mean for R&D activities at the Research Campus in Zwingenberg – and what does this mean for the enzyme production site in Cardiff? Answers from Dr. Alexander Pelzer, VP, Head of R&D BRAIN Biotech AG at the Research Campus in Zwingenberg and Dr. Andrew Ellis, VP, Fermented and Technical Director at Biocatalysts Ltd. in Cardiff, Wales.

Alexander, you have been Head of R&D at BRAIN Biotech`s Zwingenberg Research Campus since the beginning of 2023. What were your main tasks during the first months?

Alexander Pelzer: At the start of the year, we began to further sharpen BRAIN Biotech`s technology portfolio. The focus here was on integrating our research approach with the development, scaling and production expertise of our subsidiaries in the BioProducts segment. Our focus is now clearly on enzymes, microorganisms and bioprocesses. One of the reasons for this focus is to align our research and development with the goal of the entire BRAIN Biotech Group: We aim to become a leading international company for specialty enzymes and food ingredients.

In the course of updating our offering, we have also further sharpened and optimized our services for customers in the TMS business, such as in the area of tailor-made solutions. The industry expects us to provide state-of-the-art solutions in enzyme discovery and development, production strain development as well as high-yield production processes. I`m very pleased that we have embarked on this journey together with our colleagues within the Group. And I'm delighted that we are now working closely with Andrew Ellis of Biocatalysts Ltd at the interfaces of R&D and manufacturing.

Andrew, since June 2023 you´ve been responsible at Biocatalysts for the technical & operational aspects of fermentation. What exactly does this job entail?

Andrew Ellis: My role at Biocatalysts Ltd changed from management and leadership of purely technical functions –new enzyme product development and compliance – to additionally include all fermentation operations. My role is to lead delivery and continuous improvement across our fermentation business unit, and to continuously shape our fermentation strategy. This privileged role allows me to work with extremely capable and very engaged teams of scientists, technicians, engineers, regulatory experts and compliance specialists; with accountability spanning early stage enzyme development through to large scale enzyme manufacture.

We continue to be presented with exciting opportunities from our commercial teams for the development and manufacture of a wide variety of different enzymes for the food, fine chemical and life science markets.

In the second half of the year 2023, Alexander Pelzer and I, along with our respective teams, have focused our efforts to further exploit the synergies between BRAIN Biotech in Zwingenberg and Biocatalysts Ltd. The R&D capability at Zwingenberg is a powerhouse for enzyme discovery and protein engineering, complemented by their impressive expertise in strain design and fermentation process design. In this short period we have cooperatively developed new strains, developed several new enzymes candidates and shared lots of best practice for Laboratory and Operational Excellence. I look forward to the continuation of the joint journey of BRAIN Biotech Zwingenberg and Biocatalysts Ltd.

As a specialist in industrial biotechnology, BRAIN Biotech Group offers specialty enzymes and solutions for bio-based products to B2B industry. What is a so-called specialty enzyme?

Alexander Pelzer: Enzymes are referred to as specialty enzymes when they have been developed specifically to meet the needs of a particular application. In addition, specialty enzymes are primarily targeted at niche markets. Our expertise in enzyme discovery and engineering plays an important role in the development of such enzymes. We can tailor enzymes to the application. Thanks to the strategically coordinated interaction between BRAIN Biotech Zwingenberg and Biocatalysts Ltd., we are able to quickly develop these specialty enzymes to make them ready for market launch.

At Biocatalysts Ltd, the expertise is focused on development of efficient fermentation processes to manufacture new enzymes. This is aligned to their extensive knowledge in specialty enzyme markets and multi niche enzyme applications. This manufacturing and application expertise perfectly complements the enzyme discovery and strain platform capabilities at Zwingenberg.

What are the tech units´ roles in Zwingenberg and Cardiff in developing, producing and bringing them to market?

Alexander Pelzer: At our Research Campus in Zwingenberg, Germany, we focus on enzyme discovery and development. Novel enzymes can be identified in our large digital sequence database, which consists of proprietary digital metagenomic and microbial data, and is ready for sequence-driven discovery. We can also unlock new enzymes through so-called function-driven discovery using the BRAIN Bioarchive, a proprietary collection of microbial strains, as a resource.

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If the discovered enzymes do not fit perfectly to the application, we use rational protein engineering to realize a perfect fit. This is followed by an essential step: We produce these novel enzymes in our set of microbial strain platforms to analyze their producibility. The best enzyme is worthless for us if we cannot produce it. For this reason, we test producibility at an early stage in order to de-risk the development phase, knowing that we are finally aiming for an industrial application of our enzymes.

We then develop the production strains and the bioprocess – up to pre-industrial scale. If the process proves successful here, we pass on the technology and associated knowledge to our colleagues in Cardiff for scaling up.

Andrew, what happens next in Cardiff?

Andrew Ellis: Once BRAIN Biotech have developed a pre-industrial enzyme, we begin tech transfer to Biocatalysts Ltd. This requires peer-to-peer teamwork to ensure the scale-up of the process meets or exceeds appropriate commercial parameters. In essence, the tech transfer ensures that the final enzyme product is economically viable, regulatory- and quality- compliant, operationally sustainable, and exceeds the needs and wants of the customers. In reality, all of these considerations are discussed at an early stage and built into the R&D phases at Zwingenberg to allow for efficient and effective transfer.

In light of the “One-BioProducts Strategy” and the very important role Biocatalysts plays in the future product business, what further developments are planned at Biocatalysts Ltd to achieve further improvements in fermentations and to grow the enzyme business?

Andrew Ellis: We are very lucky to have an incredibly talented staff base across Biocatalysts´s four locations. Our success has been, and will be, realized through all staff working cooperatively towards our business strategy. Retention and recruitment are a key enabler in this context. Additionally, we will continue to develop our staff in order to continuously develop and sharpen our technical, operational and commercial capability.

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What makes the Cardiff site such a special place for the production of enzymes?

Andrew Ellis: What makes us unique is our highly flexible fermentation capabilities: We can quickly adapt to new requirements for speciality enzyme manufacture and efficiently implement new processes through to commercial supply. We benefit from our broad knowledge and capabilities of scaling up fermentation processes and our expertise in downstream processing. We focus on rapidly scaling up the process to commercial supply at a competitive cost.

We develop enzyme fermentation processes, with precise scalability, from as low as 250ml fermentation volume through to 5L, 50L, 750L, 10000L, 17000L and 50000L with a variety of different strains and extensive manufacturing protocols. We focus on bringing our customers’ specialty enzymes solutions targeting function, quality, regulatory compliance and required cost-in-use. At Biocatalysts Ltd, our flexible capabilities and the efficiency of their utilization make us a little different, but in a good way!

Alexander, in line with the One BioProducts strategy, BRAIN Biotech`s Research Campus in Zwingenberg has become the Group`s innovation engine. What does that mean?

Alexander Pelzer: As mentioned previously, R&D activities relate not only to the Group`s product business but also to the customer-specific solutions we offer for various industries. Our strategy is to provide state-of-the-art technological solutions for our own development projects as well as for customer projects. We develop our own technological tools, such as enzyme engineering methods and nucleases for genome editing, and combine them with the latest scientific developments, such as major advances in computer science, such as machine learning and artificial intelligence.

One of our strengths is creativity – combining methods from different areas of technology, and developing new and specific solutions to a given problem. This is actually one of our key drivers: Solving an industrial challenge through biotechnology.

Can you give us an example?

Alexander Pelzer: An important topic within the BRAIN Biotech Group is the further development of our microbial production platforms to produce specialty enzymes. For example, this includes the removal of antibiotics as selection markers. We are also jointly optimizing our strains, fermentation, and down-stream processes in terms of production yield. In doing so, we are benefiting greatly from Biocatalysts´ experience in producing commercial enzymes, and we appreciate their expertise.

These optimizations will then be applied to a number of promising specialty enzyme candidates that we have identified together with Biocatalysts and plan to develop for commercialization.

Finally, we have combined our strengths in enzyme identification: The combination of Biocatalysts´ MetXtra discovery platform and BRAIN Biotech AG`s large proprietary digital database represents a major step forward in our enzyme identification. We can now offer an even better solution for discovering enzymes.

Thank you both for answering these questions.

Questions: Dr. Stephanie Konle, BRAIN Biotech AG