Biocatalysis

* Updated version of the 2023 article.

Definition

Biocatalysis uses biological structures such as enzymes, cells or microorganisms to direct or accelerate chemical reactions. Biocatalysis typically operates under mild conditions, for example at ambient temperatures or neutral pH levels, making it often gentler and more sustainable than traditional chemical catalysis. 

Biocatalysis enables access to reactions that are not chemically feasible, while also enhancing the efficiency of existing reactions. Additionally, biocatalysts can replace environmentally harmful reagents and solvents, all the while minimising by-products. In laboratory settings, enzymatic biocatalysts can be customised for industrial applications, making synthesis reactions more selective and thus more resource-friendly and efficient.  

Current applications and opportunities

Biocatalysis is already widely used in manufacturing pharmaceuticals, agrochemicals and fine chemicals, not to mention flavourings, fragrances and foodstuffs. Examples include the production of islatravir for HIV treatment and the enzymatic cleavage of penicillin G for antibiotics manufacturing. Givaudan has developed a biocatalytic process for producing the fragrance Ambrofix, which replaces rare amber obtained from sperm whales. DSM-Firmenich uses a multi-stage enzymatic synthesis in yeast to produce the fragrance Dreamwood Base as an affordable alternative to sandalwood oil. One example from the pharmaceutical industry is Novartis’ heart failure drug Entresto. 

Thanks to their high specificity and selectivity, enzymes have become established in synthesising chiral molecules – the two mirror-image forms of identical molecules that can, however, differ in their effects. Such molecules play important roles, particularly in pharmaceuticals and in food and cosmetics production. Microorganisms optimised using synthetic biology methods and containing all the necessary enzymes enable further applications. What makes them so advantageous is the fact that they conduct synthesis through integrated, multi-stage processes as opposed to numerous individual chemical reactions. 

Advances in bioinformatics and machine learning methods have dramatically accelerated protein design and engineering, rapidly advancing biocatalysis as a field in recent years. This enables more efficient enzyme optimisation and the design of novel biocatalysts.  

Companies using biocatalysis benefit from both economic and environmental advantages. Processes often take place under mild conditions, cutting both energy consumption and operating costs. Additionally, less waste is generated and chemical requirements decrease, leading to a smaller environmental footprint. 

The high specificity and selectivity of enzymes also reduces by-product formation, thus lessening the purification requirements for the main product. Furthermore, biocatalysis enables production of complex molecules that are chemically difficult to access, such as biopolymers like proteins, nucleic acids and polysaccharides. This opens up new markets in the likes of biopharmaceuticals and sustainable materials. 

Biocatalytic processes can, for the most part, be conducted as one-pot reactions. This reduces the infrastructure requirements, while at the same time often decreasing the raw material needs too. In the chemical/pharmaceutical industry, biocatalysts could thus contribute to reshoring – the partial relocation of production facilities back to Switzerland. This would help to counter supply shortages, while also supporting compliance with sustainability requirements applicable in Switzerland. 

Challenges

Previous methods for producing biocatalysts, such as directed evolution or rational design approaches, are time-consuming. Industrial development of new enzymes is often still (too) slow, because many SMEs lack relevant expertise or their knowledge is not up to date. Promoting efficient knowledge transfer from universities to companies would address this issue. Depending on the industry sector, low public acceptance among the Swiss population for using genetically modified organisms – particularly in food production – may also hinder development. Politics and science can support biocatalysis deployment by educating the general public about the opportunities presented by genetic engineering methods, as has already been successfully done with many genetically engineered high-efficacy medications.  

Targeted research funding and financial incentives for SMEs and start-ups would also be important, through the likes of programmes supporting biocatalysis-based technologies across industries from early development stages. Switzerland currently lacks dedicated biocatalysis funding programmes.  

Focus on industry

In industry, biocatalysis methods are primarily deployed in production. Switzerland is in a good position to drive further development thanks to its strong research base and pharmaceutical and chemical industries. However, many SMEs still lack the financial and technical resources to integrate the technology. 

Employees in this field require extensive knowledge of bioinformatics, biochemistry, molecular biology, chemistry and microbiology. Knowledge of process engineering is required to scale up biocatalytic processes so that they meet industrial demands. The ability to think in an interdisciplinary manner and link knowledge from different fields of specialisation is equally important. 

The Excelzyme platform – a collaboration between Rebecca Buller’s research group and Roche that has been ongoing since 2019 – ZHAW’s Competence Center for Biocatalysis, and the “Sustainable Chemical Processes through Catalyst Design” research project at the National Centre of Competence in Research at ETH Zurich and EPFL (abbreviated to NCCR Catalysis) are making substantial efforts to intensify cooperation between science and industry. Switzerland’s return to the EU’s Horizon Europe framework programme from 2025 onwards is also extremely valuable for biocatalysis research. 

International perspective

There is fierce global competition in biocatalysis, driven primarily by the USA and Asian countries, which are investing heavily in AI research and machine learning methods. While Switzerland certainly enjoys a strong starting position thanks to its high-performing chemical and pharmaceutical industries, increased funding would help to safeguard and further expand this position in the long term. 

Future applications

Existing biocatalysis applications in the fields of pharmaceuticals, food technology and environmental technology are continuing to expand. Technological innovations will enable future design of proteins and other macromolecules for therapeutic use. One example is the COVID-19 drug Skycovion, which has already been approved in South Korea and the UK. The technology will also significantly shape diagnostics, through the likes of artificial receptors embedded in nanopores to detect small molecules. Another example is the production of artificial protein shells (capids) equipped with specific receptors to transport medications to specific locations within patients’ bodies.  

Biocatalysis harnesses enzymes and, increasingly, biological microstructures to conduct chemical reactions in environmentally friendly and efficient ways. It conserves energy, reduces waste and creates new, sustainable products. The technology is a key factor in the competitiveness of the pharmaceutical, chemical and food industries. Given just how important these sectors are to the Swiss export economy, biocatalysis has the potential to promote national innovation and to speed up Swiss industry’s transition to sustainability.