Enzyme Catalysts for Bio-Based Production

Interview with Thomas Daußmann of Enzymaster Germany about Biocatalysis Research

  • Highly specific enzyme catalysts from Enzymaster ensure sustainable and bio-based production. Source: EnzymasterHighly specific enzyme catalysts from Enzymaster ensure sustainable and bio-based production. Source: Enzymaster
  • Highly specific enzyme catalysts from Enzymaster ensure sustainable and bio-based production. Source: Enzymaster
  • Thomas Daußmann, Enzymaster Source: Enzymaster
  • The new R&D laboratories on the 17th and 18th floors of the complex of buildings in Ningbo were ready for occupancy in 2019 and, following the expansion, cover a total area of 3,000 square meters. Source: Enzymaster

Enzymaster develops and produces products for pharmaceuticals, fine chemicals and other sectors from the initial product idea to commercial ton scale production by using proprietary enzyme technologies. Accodingly, R&D services are offered along the entire value chain, from the early development of the synthetic route to a certain product to commercialization at scale on behalf of the customer. The core technologies, which are integrated into the BioEngine platform, can significantly reduce the development time and the number of the necessary experiments required to develop highly specific and innovative biocatalysts. Birgit Megges asked Thomas Daußmann, managing director of Enzymaster Deutschland, about the core competencies and goals of the still relatively young company.

CHEManager: Mr. Daußmann, Enzymaster was founded in China in 2013. What was the business idea behind it?

Thomas Daußmann: The founders represent a consortium of scientists from Singapore, Malaysia, Australia, China and Germany who decided to establish a new start-up company directly in one of the largest markets in the world, namely China, as Sino-foreign joint venture. The management of the company has been taken by Lv Zhenlin, owner of Ningbo Medicn Pharmaceuticals. As a local entrepreneur, he holds an efficient network with the local government and chemical industries nearby, which is essential for the company’s development.

In the first three years after the company was founded, most efforts were put into establishing the "BioEngine" technology platform for enzyme optimization using directed evolution techniques. The Chinese domestic market for initial business relationships was also evaluated and targeted.

What is so special about the BioEngine platform?

T. Daußmann: It enables the fast and efficient development of highly specific enzyme catalysts for biotransformations under optimal process conditions. Combining modern bioinformatics methods, namely in-silico screening, a large sequence space can be covered, which cannot be addressed by the traditional approaches in enzyme optimization.

This computer-based, rational pre-selection of the most suitable biocatalysts dramatically reduces the number of required experiments and shortens the development time to obtain innovative biocatalysts, which is an extremely critical factor, especially in the pharmaceutical industry when quickly certain amounts of a drug molecule are required to support the preclinical and clinical studies.

What are Enzymaster’s core competencies today?

T. Daußmann: Enzymaster mainly focuses on research and development, which is reflected in a quota of approx. 60% scientists in the total number of a bit over 100 employees. In addition, the founders and current directors have many years of experience in biocatalysis and directed evolution, so that requirements in the market for R&D services and product development can be optimally implemented. Besides, Enzymaster maintains close relationships, also in the form of joint ventures, with production partners in China, primarily in the Zhejiang province, which enables chemicals to be manufactured in large ton scale. The current enzyme production is done at 1,000-liter fermentation scale in our own facilities near Ningbo.

What can enzymatic technologies generally achieve nowadays?

T. Daußmann: In today's world, tailor-made biocatalysts are the best choice for the sustainable and bio-based production of substances for a wide variety of applications such as pharmaceuticals, agrochemicals, flavors and fragrances, nutritional supplements like vitamins, cosmetics and fine chemicals. With the help of the directed evolution method, which was awarded the Nobel Prize for Frances Arnold from Caltech in 2018, enzymes can be effectively optimized and made ready for new applications. Many new classes of biocatalysts thus complement or replace chemical synthesis with highly selective C-C linkages, regio- and stereospecific functions, which are often not possible with traditional methods. In particular, non-productive synthetic steps that only serve to protect functional groups or to activate non-reactive groups can often be avoided. This shortens synthetic routes and generates fewer by-products, which enables more efficient and resource-saving manufacturing processes.

Enzymaster Deutschland was founded in 2018 and the international business was included in the company's further focus. Why did you choose Germany?

T. Daußmann: Germany, and here in particular Düsseldorf with many industries in health, home and personal care sectors in immediate vicinity, offers an ideal location to serve the European markets from a central location. Many trade fairs and scientific conferences also take place in Germany or neighboring countries. The Rhineland with the universities and research institutions in Cologne, Düsseldorf, Jülich and Aachen, among others, is also a hotspot in the academic biotech scene and offers excellent opportunities for cooperation.

In addition, of course, as a shareholder of Enzymaster in Ningbo, I have my personal home and extensive network here in the Rhineland region.

What tasks does the German subsidiary cover?

T. Daußmann: The primary aim of the German subsidiary is to expand and support Enzymaster's international business. Because of the distance, language barrier and different time zones, it is very important for a company located in China to serve the European and American customers directly from Europe or North America instead of China. Being close to the customer is very significant for our high-tech services and creates a higher level of trust for long-term cooperation.

Which markets do you serve with your offer?

T. Daußmann: Based on the founders' expertise, Enzymaster initially focused on the pharmaceutical market, but also worked with customers in the food & feed area since several years. For example, beta-alanine and vitamin B5 are interesting products that are already produced on a multi-ton scale using in-house developed enzyme technology. The advantage of the BioEngine technology platform is, of course, that the enzyme optimization programs can also be applied to any other markets in which enzymes play or may play a role in the future. For this reason, Enzymaster is currently expanding its market to other areas, such as the flavor and fragrance industry, as well as in home and personal care fields.

In which areas do you see the greatest development potential?

T. Daußmann: In our opinion, biocatalysis is very well established in the pharmaceutical industry, whereas chemical processes are often given higher priority in other industries. However, in the course of the sustainability discussion, the use of enzymatic methods is fundamentally becoming increasingly interesting.

In the food sector, however, the GMO problem is an obstacle to fermentative approaches; biocatalysis with isolated enzymes based on regenerative raw materials can be a valuable alternative on the way to sustainable “green” production.

In terms of technology, our focus is to establish novel enzyme classes in addition to the already well-established ketone reductases and transaminases for industrial applications. The integration of artificial intelligence is also a hot topic in order to make enzyme optimization programs more effective and, above all, much faster.

What are Enzymaster's future plans?

T. Daußmann: First of all, we would like to continue concentrating on expanding the Düsseldorf subsidiary serving the business development in Europe. In addition to pharmaceuticals, we want to get involved with our biocatalysis applications in other industries which are already mentioned above. The establishment of an R&D site in Europe is currently under discussion, too, decisions will probably be made in the course of 2020. Other locations within Europe are not excluded per se, but we will probably start with hiring employees or consultants in corresponding European countries first. Outside of Europe, we plan to work more closely with distributors or agents in the first stage before considering another subsidiary there, for example in the United States. In addition, the existing location in Singapore is also to be further expanded in order to serve the dynamically growing markets in Southeast Asia more efficiently.


ABOUT

Thomas Daußmann is co-founder of Enzymaster (Ningbo) Bio-Engineering, executive VP International Business and managing director of Enzymaster Deutschland. With a PhD in microbiology, he has more than 20 years of experience in the field of biocatalysis research and industrial application, as well as in the establishment of start-ups and related subsidiaries (founder Jülich Fine Chemicals; MD & VP Codexis Laboratories Singapore).

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