Unlocking the Power of Biocatalysis for Complex Molecules and Novel Modalities
Meeting the challenge of next-generation therapeutics with tailored enzyme solutions
The pharmaceutical and life science industries are in the midst of a transformation. As therapeutic modalities become more sophisticated - spanning chiral small molecules, nucleoside analogues, oligonucleotides, peptides, and antibody-drug conjugates (ADCs), the complexity of chemical synthesis is increasing dramatically. Biocatalysis is now stepping in to address limitations that traditional synthetic chemistry can no longer overcome efficiently or sustainably.
Biocatalysis Beyond the Basics
No longer limited to simple transformations, biocatalysts are now being engineered for highly selective reactions including:
- Late-stage functionalisation using unspecific peroxygenases (UPOs), delivering superior total turnover numbers versus classical P450 systems.
- Enzymatic modifications of nucleoside analogues and oligonucleotide synthesis, offering alternative routes to high-fidelity nucleic acid production.
- Incorporation of non-canonical amino acids into peptides and proteins, expanding the chemical space available for drug design.
- ATP-dependent transformations, now feasible at scale thanks to innovations in ATP cofactor recycling.
- The mainstreaming of iron-sulphur cluster enzymes, previously difficult to stabilise or scale.
These breakthroughs are redefining what's possible in the synthesis of next-generation pharmaceuticals.
A New Era of Process Design
As the scope of enzymatic reactions grows, so does the complexity of bioprocesses. The industry is moving beyond single-step conversions toward multi-enzyme cascade reactions, where several biocatalysts act sequentially or simultaneously to convert starting materials into high-value products. Achieving this requires:
- Predictive modelling to guide enzyme selection and reaction compatibility.
- Strain co-expression systems that allow multiple enzymes to be produced within a single host organism.
- One-pot strategies and flow biocatalysis, enabling more efficient, scalable, and continuous production.
- Enzyme immobilisation techniques to improve catalyst stability and reuse, decreasing cost of goods.
However, success depends on more than the enzymes alone. Selecting the right host strain is now critical, particularly as E. coli, once the default chassis, often fails to meet the needs of more complex biocatalysts. The ability to develop or adapt microbial production strains to handle specialised cofactors, protein folding requirements, post-translational modifications or secretion pathways is a competitive advantage in this new landscape.
BRAINBiocatalysts: Enabling Next-Generation Therapeutics
At BRAINBiocatalysts Life Science Solutions, we are helping customers navigate this complexity through a fully integrated approach - merging enzyme discovery and engineering, strain engineering, and scale-up. Our expertise includes:
- Custom enzyme cascades tailored to specific pharmaceutical targets.
- Protein Engineering in Bacillus or Komagataella (formerly known as P. pastoris) of enzymes that are difficult to express in E. coli.
- Advanced (production) strain development and co-expression systems using yeast, fungi, and bacteria.
- Plug & Produce platforms with proven industrial scalability for fast evaluation of enzyme expression and feasibility.
- Support for cofactor-dependent enzyme systems through robust bioprocess engineering.
As the industry pushes toward greater molecular diversity and process efficiency, biocatalysis will be a driving force. Partnering with experts who can deliver from bench to 10,000 L fermentation makes the difference between proof of concept and commercial success.
