03 Oct 2019

The food industry is constantly looking at how to produce novel products that promote their brand and leverage the new trends addressing consumer concerns for healthier products. In a market with a slow product innovation cycle, looking for options that can speed up the time frame of launching new products can have a significant commercial impact. In this article, Biocatalysts Ltd discusses how novel enzymes can be cost effectively identified and produced to support and drive innovation in meeting the growing consumer demands on the food industry.

It is well known that enzymes allow companies to access new chemistries and the role that they play in improving process conditions in the food ingredient, fine chemical and flavour industries. There are numerous benefits provided by enzymes; they can accelerate a biochemical reaction, produce new and exciting natural flavours, modify texture, increase yields and modify chemical composition to produce novel products or help in reducing process costs. Enzymes are natural, non-toxic, biodegradable and easily inactivated. They are classed as a processing aid in many countries and therefore contribute to a “clean label” product.

There are six classes of enzymes; oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. Out of the millions of enzymes available in nature only a fraction have been characterised, with only a small proportion of those being commercialised. The chance, therefore, of the perfect enzyme for your process being commercially available is slim. Added to that there are only a limited number of commercial enzyme manufacturers in the world.

So how do you access this diverse pool of enzymes to gain the process advantages that they can provide? This was a question we asked ourselves here at Biocatalysts and we have been working diligently to solve this conundrum and provide a service that uses all the recent exciting developments in biotechnology.

Recent Developments in Biotechnology

Biocatalysts Ltd is an innovative global biotechnology company that has been producing speciality enzymes for the food and related industries for over 35 years. We pride ourselves on providing in depth technical knowledge and superb customer service. We do this by using the best technologies available and keeping abreast of the newest advancements impacting the biotech industry. Historically, identifying and commercialising a novel enzyme was a long and costly process. At Biocatalysts, we realised with the recent advances in the manipulation of mega data and new tools available to identify genes and manipulate them into expression systems, that we could reduce the cost and time of novel enzyme discovery, development and manufacture. Our goal was to provide a new system that would allow an enzyme to be identified, developed and commercialised within months instead of years and at a more accessible cost.

It is believed that greater than 99% of microbes in nature cannot yet be cultivated in the laboratory. Consequently, using traditional techniques means that we are unable to access >99% of this valuable genetic heritage. New metagenomic techniques make it possible to DNA sequence directly from environmental samples, avoiding the need for culturing the organisms in a laboratory.

Biocatalysts invested in both people and equipment, and within 5 years we had developed a novel process that included a bespoke software system, MetXtra™. MetXtra, is a powerful bioinformatics platform that is able to screen millions of sequences in order to identify new enzymes based on either customer derived target sequences or on functionality (for example an enzyme that is active at high or low temperature or pH) in a few hours. The platform does this by identifying complete novel enzymes within large metagenomics DNA sequence libraries. We have combined our own metagenomic libraries with open source databases, giving us access to over 350 million enzyme gene sequences. As DNA sequencing is no longer necessary, screening can be completed in minutes rather than days. Even wild-type enzymes, which have been excluded from industrial use due to impracticability, can now be exploited.

To further maximise the successful commercial scale up of the enzyme, Biocatalysts developed a Design for Manufacture (DFM) set of criteria, by applying more than 20 biochemical and biophysical algorithms to filter the enzyme sets to select the most viable candidates. This resulted in the early stages of enzyme discovery being reduced from years to a few weeks and enables the supply of laboratory grade enzyme samples for customer evaluation at a significantly reduced time and cost. Once the new enzyme has been selected, Biocatalysts works with the customer to scale up. Being able to provide scale up and manufacture capabilities means there are no delays in technical transfer, minimising the timelines to production of commercially available material. This means, for example, a new novel enzyme for galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS) production, or improving texture or flavour of plant-based proteins can be developed and scaled up in months instead of years. Thus, giving companies access to these enzymes in realistic time frames, providing them the opportunity to promptly produce new products in response to market trends.

In recognition of Biocatalysts’ drive and enlightened approach to providing the best Enzyme Development and Manufacturing solutions to our customers, we are delighted to have been awarded the prestigious Queens’ Award for ‘Enterprise in Innovation’. This is in recognition of our innovative approach and commitment to creating a unique offering to the market.

At Biocatalysts, we have always had an ethos of sharing our technical knowledge and expertise in enzyme development and manufacture. We pride ourselves on supporting our customers from proof of concept right through to full scale enzyme commercialisation. Daren Bryce, Commercial Director, explains how Biocatalysts support their customers: ‘We deliver solutions for customers who want their products to stand out in the market in terms of flavour, texture, improved health benefits and clean labelling. As well as offering standard solutions, we discuss with customers their process requirements and development opportunities to provide a custom enzyme solution for their application’.

Case Study

Biocatalysts Ltd is part of the LIPES project, (this project has received funding from the Bio Based Industries Joint Undertaking under the European Union’s Horizon 2020 research and innovation program under grant agreement No 720743) the aim of the project is to create a new enzymatic process to produce selected commercially important fatty acids at an overall lower variable cost than the current processes. Biocatalysts’ challenge was to identify and produce novel lipase enzyme(s) for different types of oils. We produced a panel of lipase enzymes based on the specificity of the oil substrate used for the hydrolysis reaction. We followed our ‘Design for Manufacture’ (DFM) approach to ensure that any enzymes selected had already been evaluated at the start of the project for its operational (high production yield and downstream processing) and regulatory requirements. The panel of new lipases was sent to Oleon (responsible in the project for scale up of the enzymatic process for commercial production of fatty acids), for evaluation, who confirmed one of the enzymes met the performance parameters.

We then scaled up the enzyme to produce a more commercially representative sample via small scale fermentation and Down Stream Processing (ensuring both processes would be scalable and transferable to full scale manufacture of the enzyme). The larger sample produced was sent to Oleon for further testing for hydrolysis of the specific oil at laboratory scale and at small scale reactor level. Results from Oleon confirmed the new lipase was suitable for the hydrolysis of this specific oil and Biocatalysts were requested to scale up the process to produce the new enzyme at small commercial scale to provide enough enzyme for process scale up trials.

This case study outlines the capabilities of Biocatalysts’ Enzyme Discovery and Manufacture process for identifying a gene sequence, cloning it, expressing it and producing a viable enzyme with specific activity that is suitable for commercialisation.

Future Challenges

Never to sit on our laurels, Biocatalysts is always looking for the next challenge. We identify the newest technologies available and introduce them into our processes to continually increase our technical capabilities and improve our offering. The largest and most recent investment to date being a £6 million extension, housing a new 10m3 fermenter, high tech mini fermenters and downstream processing. This investment will increase the company’s fermentation capacity more than 10-fold and considerably reduce development time, ensuring that Biocatalysts strives to keep our commitment to exceeding our customers’ enzyme expectations.

Conclusion

Enzymes are all around us, they are at the core of virtually all of nature’s chemical processes. This means they are diverse and abundant giving us a vast pool of material to select from to develop enzymatic solutions. At Biocatalysts, we have combined our knowledge of enzymes with the latest technologies and developed a unique Enzyme Development and Manufacturing process that is capable of accessing this data providing a practical, time bound solution to identifying and manufacturing custom enzymes to fit specific customer processes. If you are looking for ways to differentiate your brand, develop novel products or improve your process, why not contact us for a consultation.

Source: Biocatalysts Ltd